UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`TEVA PHARMACEUTICALS USA, INC.,DR. REDDY’S
`LABORATORIES, LTD. AND DR. REDDY’S
`LABORATORIES, INC.,
`
`Petitioner
`v.Petitione
`
`rs, v.
`
`MONOSOL RX, LLC,LTD., Patent Owner.
`
`Patent Owner
`
`Case No. IPR2016-XXXXX
`
`DECLARATION OF METIN ÇELIK, Ph.D. IN SUPPORT OF PETITION
`FOR
`INTER PARTES REVIEW OF U.S. PATENT NO. 8,603,514
`
`“UNIFORM FILMS FOR RAPID DISSOLVE DOSAGE
`FORM INCORPORATING TASTE-MASKING
`COMPOSITIONS”
`
`DRL - EXHIBIT 1003
`DRL
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`MonoSol2003-0001
`
`Dr. Reddys v. MonoSol
`IPR2016-01111
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`TEVA PHARMACEUTICALS USA, INC.,DR. REDDY’S
`LABORATORIES, LTD. AND DR. REDDY’S
`LABORATORIES, INC.,
`
`Petitioner
`v.Petitione
`
`rs, v.
`
`MONOSOL RX, LLC,LTD., Patent Owner.
`
`Patent Owner
`
`Case No. IPR2016-XXXXX
`
`DECLARATION OF METIN ÇELIK, Ph.D. IN SUPPORT OF PETITION
`FOR
`INTER PARTES REVIEW OF U.S. PATENT NO. 8,603,514
`
`“UNIFORM FILMS FOR RAPID DISSOLVE DOSAGE
`FORM INCORPORATING TASTE-MASKING
`COMPOSITIONS”
`
`DRL - EXHIBIT 1003
`DRL
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`MonoSol2003-0001
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`Dr. Reddys v. MonoSol
`IPR2016-01111
`
`
`
`TABLE OF CONTENTS
`
`I.
`
`II.
`
`INTRODUCTION
`
`QUALIFICATIONS
`
`A.
`
`B.
`
`C.
`
`D.
`
`Education and Work Experience
`
`Professional Affiliations, Activities, and Awards
`
`Publications and Educational Involvement
`
`Prior Testimonies
`
`III.
`
`SCOPE OF THE WORK AND COMPENSATION
`
`A.
`
`Bases for Opinion and Materials Considered
`
`IV.
`
`SUMMARY OF OPINIONS
`
`V.
`
`LEGAL STANDARDS
`
`VI.
`
`PERSON OF ORDINARY SKILL IN THE ART
`
`VII.
`
`THE ‘514 PATENT
`
`A.
`
`B.
`
`Priority Date of the ‘514 Patent
`
`The Challenged Claims of the ‘514 Patent
`
`VIII.
`
`BACKGROUND AND TUTORIAL
`
`A.
`
`B.
`
`Polymers
`
`Particles
`
`Page
`
`1
`
`1
`
`3
`
`4
`
`5
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`6
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`6
`
`7
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`7
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`13
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`15
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`15
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`15
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`16
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`21
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`21
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`24
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`-i-
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`TABLE OF CONTENTS
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`(Continued)
`
`C.
`
`D.
`
`E.
`
`F.
`
`Role of Viscosity
`
`Drying of Suspensions
`
`Role of Uniformity in Drug Formulations
`
`Flavoring of Pharmaceutical Formulations
`
`IX.
`
`SCOPE AND CONTENT OF THE PRIOR ART REFERENCES
`
`A.
`
`B.
`
`WO 200/42992 (Chen) (Ex. 1005)
`
`U.S. Patent No. 8,603,5147,067,116 (Bess) (Ex. 1004)
`
`Case IPR2016: Unassigned
`
`EXPERT DECLARATION OF JAYANTH PANYAM, Ph.D.
`
`25
`
`29
`
`31
`
`33
`
`33
`
`33
`
`40
`
`C.
`
`CA 2274910 (Cremer) (Ex. 1006)
`
`X.
`
`INVALIDITY OF THE ‘514 PATENT
`
`41
`
`42
`
`EXHIBIT NO. 1003 Page 1 of 58
`
`A.
`
`B.
`
`Claims 1 and 62 of the ‘514 Patent are Obvious over Bess in view of Chen
`42
`
`A POSA would combine the Teaching of Bess and Chen along with the
`DRL - EXHIBIT 1003
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`Knowledge in the Art 46
`
`C.
`
`D.
`
`E.
`
`F.
`
`Additional Limitations in Independent Claims 1 and 62 do not render those
`claims Nonobvious over Bess and Chen 47
`
`The Dependent Claim Limitations Do Not Render the ‘514x Asserted Claims
`Nonobvious over Bess and Chen
`47
`
`Claims 1 and 62 of the ‘514 Patent are Obvious over Chen and Cremer 49
`
`A POSA would combine the Teachings of Chen and Cremer along with the
`Knowledge in the Art 54
`
`-ii-
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`TABLE OF CONTENTS
`
`(Continued)
`
`G.
`
`H.
`
`Additional Limitations in Independent Claims 1
`and 62 do not render those claims Nonobvious over
`Chen and
`Cremer
`
`55
`
`The Dependent Claim Limitations do not render the those Claims
`Nonobvious over Chen and Cremer.
`55
`
`XI.
`
`CONCLUSION
`
`57
`
`-iii-
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`I, Metin Çelik, Ph.D. declare as follows:
`
`I.
`
`INTRODUCTION
`
`1.
`
`My name is Jayanth PanyamMetin Çelik. I have been retained by
`
`counsel for Teva Pharmaceuticals USA, Inc. (“Teva”). I understand that Teva is
`
`petitioning for inter partes review of U.S. Patent No.Petitioner Dr. Reddy’s
`
`Laboratories, Inc. of 107 College Road East, Princeton, NJ 08540 and Dr.
`
`Reddy’s Laboratories, Ltd. of 8-2-337, Road No. 3, Banjara Hills,
`
`Hyderabad, India 500034) (collectively, “Dr. Reddy’s”) to provide opinions
`
`relating to U.S. Patent 8,603,514 (“the “’514 patent”), which is assigned to
`
`Monosol RX, LLC (“Monosol‘514 Patent”). I further understand that Teva is
`
`requestingDr. Reddy’s requests that the United States Patent and Trademark
`
`Office (“USPTO”) cancel certain claims 1-3, 9, 15, 62-65, 69-73, and 75 of the
`
`’‘514 patent as unpatentable over Bess in view of Chen, and Chen in view of
`
`Cremer. This. I submit this expert declaration, which addresses and supports
`
`Teva’sthe petition of Dr. Reddy’s.
`
`I.Qualifications and Background
`II.
`QUALIFICATIONS
`A.Education and Experience; Prior Testimony
`1.My background, qualifications, and experience related to my opinions
`
`expressed in this report are given in my curriculum vitae attached as Ex. 1036.
`
`2.
`
`I received my Bachelor’s degree in Pharmacy in 1997 from the T.N.
`
`--
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`Dr. MGR Medical University. I continued my education at Banaras Hindu
`
`University and received my Masters degree in Pharmaceutics in 1999. In 2003,
`
`I received my Ph.D. in Pharmaceutical Science from the University of Nebraska
`
`Medical Center.am currently the President of Pharmaceutical Technologies
`
`International, Inc. (“PTI”), a company that I founded in 1997. PTI
`
`develops management tools, databases and expert systems for the
`
`pharmaceutical industry worldwide and provides expert consultant
`
`services to various international pharmaceutical, food, excipient and
`
`equipment companies and to law firms throughout North America.
`
`3.
`
`I have more than nine years of experience working in the
`
`pharmaceutical sciences. I am currently a professor with tenure at the
`
`University ofSince 2008, I am also a Research Professor of Pharmaceutical
`
`Technology at the College of Pharmacy, Near East University in Cyprus
`
`where I have established a tabletting research center.
`
`--
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`Minnesota, in Minneapolis.
`
`DECLARATION OF JAYANTH PANYAM EXHIBIT NO. 1003 Page 2 of 54
`Over the past thirty years, working in industry, academia, and as a
`4.
`
`consultant, I have been continuously involved in the development and
`
`formulation of pharmaceutical products. I have also provided expert
`
`consultant services to the Food and Drug Administration (“FDA”).
`
`5.
`
`My involvement in the formulation and process of pharmaceutical
`
`products has given me specialized expertise in the areas of solid dosage
`
`forms, integrated compaction research systems, the theory and practice of
`
`pharmaceutical compaction, excipient functionality testing, multiunit dosage
`
`form development, artificial neural networks, design and development of
`
`pharmaceutical formulation and processing expert systems, preformulation
`
`and compaction databases and the development of Management Information
`
`Systems for FDA inspection preparations and general project management
`
`purposes.
`
`6.
`
`With respect to formulation and process of oral dosage forms, my
`
`practical experience began at Novartis (formerly known as Sandoz) –
`
`Switzerland in 1984. My knowledge in this area continued to develop during
`
`my time at Novartis, in Switzerland and Turkey, and then as a professor in
`
`the College of Pharmacy at Rutgers University in Piscataway, New Jersey.
`
`As a member of the faculty at the latter institution, I lectured in this field
`
`--
`
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`(within and outside the University) and conducted research both as an
`
`advisor to a Ph.D. project and as a consultant to the pharmaceutical
`
`industry.
`
`--
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`MonoSol2003-0009
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`4.Throughout my career, I have published sixty peer-reviewed articles and five book
`
`chapters related to pharmaceutical sciences. I have also been invited to give presentations
`
`at more than thirty national meetings, including “Targeting circulating tumor cells and
`
`metastases in breast cancer,” “Nanoparticles for Tumor- targeted Drug Delivery:
`
`Challenges and Opportunities,” and “PLGA-induced inflammation is a double-edged
`
`sword.”
`
`A.
`
`7.
`
`Education and Work Experience
`
`I earned my B.Sc. (Hons.) degree in Pharmacy from
`
`Hacettepe University in Turkey in 1979.
`
`8.
`
`I was awarded a Ph.D. degree in Pharmaceutical Technology
`
`by the Department of Pharmaceutical Technology, School of Pharmacy,
`
`De Montfort University (formerly known as Leicester Polytechnic), the
`
`United Kingdom, in 1984.
`
`9.
`
`After completing my Ph.D. in 1984, I took a position in the
`
`Galenical R&D Department at Novartis in Switzerland, where I was
`
`involved in pharmaceutical technology research and development. I was
`
`then promoted to Development Co-ordinator, Galenical R&D at Novartis
`
`in Turkey, where I was responsible for establishing a pharmaceutical
`
`research department.
`
`10.
`
`In 1986, I joined Smith Kline & French Laboratories (presently
`
`known as GlaxoSmithKline) in Swedeland, Pennsylvania, where I developed
`--
`
`DECLARATION OF
`JAYANTH
`
`MonoSol2003-0010
`
`
`
`and established the first state-of-the-art Compaction Simulator System in
`
`the Western hemisphere.
`
`11.
`
`In 1988, I joined the faculty at the College of Pharmacy, Rutgers
`
`University, where I stayed until 1997. During my tenure at Rutgers, I taught
`
`various courses to both undergraduate and graduate students that focused
`
`on the theory and practice of pharmaceutical formulation and process
`
`development. Such
`
`--
`
`DECLARATION OF
`JAYANTH
`
`MonoSol2003-0011
`
`
`
`courses included Drug Delivery, Problems in Pharmaceutics, and
`
`Pharmaceutical Processes and Equipment.
`
`12.
`
`At Rutgers, in my position as Director of Pharmaceutical
`
`Compaction Research Laboratory & Information Center, I developed a
`
`second Compaction Simulator System. The Compaction Simulator System
`
`at Rutgers was the first to be developed in academia in the U.S.A., and
`
`consequently established Rutgers as an internationally recognized
`
`pharmaceutical research centre.
`
`13.
`
`Between 2004 and 2008, I was a Pharmaceutical Processing
`
`Research Professor at the Department of Industrial Engineering
`
`(2004-2008) at Rutgers where I was involved in the development of a
`
`Process Analytical Technology (PAT) program at Rutgers.
`
`B.
`
`Professional Affiliations, Activities, and Awards
`
`14.
`
`5.I am or have been a member of the following professional
`
`organizations: the American Association of Pharmaceutical Scientists, the
`
`Controlled Release Society, and (AAPS), the New Jersey Pharmaceutical
`
`Association of Science and Technology (NJPhAST), the American Association
`
`of Colleges of Pharmacy (AACP), and the Ankara Chamber of Pharmacists
`
`(ACP).
`
`15.
`
`6.I am named as an inventor on one issued patent entitled
`
`“Nanoparticles for imaging and treating chlamydial infection,” as well as five
`--
`
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`MonoSol2003-0012
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`pending patent applications and invention disclosures.have been extensively
`
`involved with several groups in the AAPS. For example, from 1995 to 1998, I
`
`held the position of chair of the AAPS Process Development Focus Group. I
`
`am also a founder and the former chair of the AAPS
`
`7.I have previously testified as an expert in a deposition.
`
`B.Bases for Opinions and Materials Considered
`
`8.Ex. 1037 includes a list of the materials I considered, in addition to my
`
`experience, education, and training, in providing the opinions contained herein.
`
`--
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`DRL - EXHIBIT 1003
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`MonoSol2003-0013
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`
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`Excipients Focus Group and a founder and the former chair of the AAPS
`
`Expert Systems Focus Group. I have also served as a member of the
`
`Pharmaceutical Technology Section Programming Committee.
`
`16.
`
`In 1991, 1993, and 1994, I received the Faculty Academic
`
`Service Increment Program Award in recognition of my service at
`
`Rutgers.
`
`17.
`
`I am also listed in the Who’s Who in Science and Engineering
`
`(1995). In 1996, I received the Commission of Science & Technology of New
`
`Jersey Award.
`
`18.
`
`While at Rutgers, I also received more than fifty grants from a
`
`wide variety of pharmaceutical companies, including Glaxo and
`
`SmithKline Beecham, totaling more than $1.1 million.
`
`C.
`
`Scope of WorkPublications and Educational Involvement
`
`19.
`
`I have organized over thirty national and international
`
`symposia and short courses. I have published a book, nine book chapters,
`
`and more than thirty articles relating to pharmaceutical formulation and
`
`processing issues, along with numerous abstracts and papers presented at
`
`scientific conferences.
`
`20.
`
`I have also served as an editorial board member and/or reviewer
`
`for journals such as Pharmaceutical Technology, Drug Development and
`
`Industrial Pharmacy, the European Journal of Pharmaceutical Sciences, and
`--
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`DRL - EXHIBIT 1003
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`MonoSol2003-0014
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`the International Journal of Pharmaceutics. In addition, I have made over
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`200 presentations at
`
`--
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`industry, academic, national and international meetings, and conferences,
`
`most of which by invitation.
`
`D.
`
`Prior Testimonies
`
`21.
`
`Since 2000, the following are a list of matters in which I have
`
`testified at trial or by deposition. (See Appendix A to Exhibit A,
`
`Curriculum Vitae).
`
`22.
`
`Attached to this Declaration as Appendix A is a copy of my
`
`Curriculum Vitae detailing my professional expertise in relation to the
`
`fields of pharmaceutical formulation and process development.
`
`III.
`
`SCOPE OF THE WORK AND COMPENSATION
`
`23.
`
`9.I have been retained by Teva as a technical expert in this
`
`matter toasked by counsel for Dr. Reddy’s to provide opinions relating
`
`to U.S. Patent 8,603,514 (“the ‘514 Patent”)
`
`24.
`
`provide various opinions regarding the ’514 patent. I receive $750
`
`per hourI am being compensated for my services and $1,150 for time spent
`
`testifying at deposition, hearing, or trial. Notime spent on this matter at my
`
`usual consulting rate of $625.00 per hour. My compensation does not
`
`depend on the outcome of this matter. No part of my compensation is
`
`dependent upon my opinions given or the outcome of this case. I do not have any
`
`other current or past affiliation as an expert witness or consultant with TevaDr.
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`--
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`Reddy’s. I do not have any current or past affiliation with Monosol RX, LLC,
`
`or any of the named inventors on the ‘514 Patent.
`
`--
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`A.
`
`Bases for Opinion and Materials Considered
`
`25.
`
`Exhibit 1035 includes a list of the materials I considered, in
`
`addition to my experience, education, and training, in providing the opinions
`
`contained herein.
`
`IV.
`
`SUMMARY OF OPINIONS
`
`26.
`
`As explained in detail in Section VIII, it is my opinion that all of
`
`the challenged claims (1-3, 9, 15, 62-65, 69-73 and 75) of the ‘514 patent
`
`would have been obvious in view of the prior art, including the references
`
`cited below, which collectively teaches and motivates a person of ordinary
`
`skill in the art to make and use the same film formulation compositions that
`
`are claimed by the ’514 patent.
`
`II.Summary of Opinions
`27.
`10.It is my opinion that the challenged claims – claims 1-3, 9, 15,
`
`62-65, 69-73, and 75 – are obvious under 35 U.S.C. § 103 in view of the prior
`
`art, including the references cited below, which collectively teaches and
`
`motivates a person of ordinary skill in the art to make and use the same film
`
`formulation compositions that are claimed by the ’‘514 patent.
`
`28.
`
`11.I have reviewed the uniform thin film drug delivery prior art, and
`
`find that one of ordinary skill in the art would have understood that the Bess1 and
`
`1 Bess, Ex. 1004.1004
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`--
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`Chen2 references, and as well as the Chen and Cremer3 reference,references
`
`render obvious the challenged claims of the ’514 patent.
`
`2 Chen, Ex. 1005.1005
`3 Cremer, Ex. 1006.1006
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`--
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`29.
`
`12.The allegedly inventive concepts of the ’514 patent were all well-
`
`known in the prior art. It was known at the time of the alleged invention of the
`
`’‘514 patent that uniform suspensions are important for use in drug delivery.
`
`Dispersion of pharmaceutical actives uniformly throughout a suspension was well
`
`known in the art. Uniformity was known to be challenging for those compounds
`
`that were not readily soluble, thereby forming suspensions. It would have thus
`
`been obvious by the priority date to use uniform dispersion of pharmaceutical
`
`actives throughout a suspension.
`
`30.
`
`13.It was also known that uniform suspensions of particulate agents
`
`(before or after casting) were highly dependent on viscosity. One of skill in the art
`
`would have understood that uniformity in film formulations meant for human use
`
`was expected and readily achieved. (See, e.g., Ex. 1013, The Theory and Practice
`
`of Industrial Pharmacy, at 56-57, 358-359, 368-369.)4 The ’233 patent5 discloses
`
`that homogeneous suspensions of various polymers, including vinyl acetate and
`
`cellulose, were used for cast films. (Ex. 1022, ‘233 patent, at Abstract.) These
`
`films were also dried and considered to be homogenous. (Id. at 4:59-5:3.) Further,
`
`it was well known in the art that the uniformity of particulates in a suspension was
`
`4 Ex. 1013, The Theory and Practice of Industrial Pharmacy (Lachman et al., eds., 3d ed.
`1986).
`4 Ex. 1013, The Theory and Practice of Industrial Pharmacy (Lachman et al.,
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`--
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`directly related to the suspension’s viscosity. (Ex. 1013, The Theory and Practice
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`4 Ex. 1013, The Theory and Practice of Industrial Pharmacy (Lachman et al.,
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`of Industrial Pharmacy, at 484.) The uniformity could also be affected by the
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`mixing time and speed used for making a suspension. (Id. at 491-492.) Stoke’s
`
`law, well known in the art by 2001, taught that settling of particulates in a
`
`suspension is directly related to, among other things, the density of the particles
`
`and the viscosity of the solution. (Ex. 1014, Theory of Pharmaceutical Systems,
`
`Volume II: HeterogeneousHeterogenous Systems, at 9.)65 Therefore, one of skill
`
`in the art would understand that to achieve a desired uniformity, particularly for
`
`pharmaceutical particles, one would necessarily consider the viscosity of the
`
`suspension.
`
`31.
`
`14.It was well known that uniform particle distribution within a film,
`
`whether cast or sprayed onto a drug dosage form, such as a tablet, was critical.
`
`(Ex. 1013, The Theory and Practice of Industrial Pharmacy, at 362-364.) One
`
`way to achieve uniformity of particulates, such as in the case of colorants, was to
`
`“mill[]” the colorant in the coating solution. (Id. at 369.) It was also well known
`
`that the viscosity of the coating solution would affect the “uniform dispersion of
`
`the colorants[’]” particle dispersion. (See id. at 369; Ex. 1014, Theory of
`
`Pharmaceutical Systems, Volume II: Heterogeneous Systems, 1973, p. 9.)
`
`32.
`
`15.It was well known that one could vary the viscosity of a
`
`suspension. (Ex. 1013, The Theory and Practice of Industrial Pharmacy, at
`
`6 Ex. 1014, Cartensen, Theory of Pharmaceutical Systems, Volume II: Homogenous Systems
`(1973).
`
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`484,491-492.)
`
`16.
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`--
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`Lachman, for example, discloses that adding specific polymers, which have different
`
`viscosities, could “cause loss of . . . the tendency to agglomerate.” (Id. at 654-55.) In other
`
`words, this could increase uniformity of the particles. Chen7, too, taught that “the viscosity
`
`of the hydrocolloid” is important to the properties of the composition. (Chen, Ex. 1005, at
`
`13:1-6, Tables 9a, 9b.) Multiple polymers with various viscosities were available and
`
`could be used in films. (Ex. 1013, The Theory and Practice of Industrial Pharmacy, at
`
`365-368.)
`
`33.
`
`17.It would have also been obviousA person of ordinary skill in the
`
`art would know by the priority date that one of several methods to achieve
`
`rapid dissolution of pharmaceutical actives is to employ mucoadhesive,
`
`uniform, oral films comprising polymers to achive rapid dissolution of
`
`pharmaceutical actives by the priority date. Mucosally- adhesive, oral dosage
`
`forms made of water- soluble polymers used to deliver therapeutic agents have
`
`been known since at least 1997. (See Ex. 1023, Guo & Zerbe, “Water soluble
`
`film for oral administration,” Proceedings of the 24th Int’l Symposium on
`
`Controlled Release of Bioactive Materials, 227 (1997) (“Guo”), at 227; Ex. 1024,
`
`Cassidy et al., “Controlled buccal delivery of buprenorphine,” J. Controlled
`
`Release, 25:21-29 (1993) (“Cassidy”) at 21-22; Ex. 1006, Cremer et al., Canad.
`
`Pat. No. CA2274910 (“Cremer”) at 10.10; Ex. 1027, U.S. Patent No. 5,948,430
`
`to Zerbe et al., Abstract; and Ex. 1033, WO2001/70194 to Park et al.,
`
`7 Chen, Ex. 1005.
`
`--
`
`DRL - EXHIBIT 1003
`DRL014
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`MonoSol2003-0024
`
`
`
`Abstract)
`
`34.
`
`18.Some mucosally-adhesive films left an unpleasant residue in an
`user’s
`
`--
`
`DRL - EXHIBIT 1003
`DRL014
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`MonoSol2003-0025
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`
`
`mouth after dissolution. (Ex. 1023, Guo at 227.) Rapidly dissolving films were
`
`developed to alleviate this problem because they were manufactured without an
`
`adhesive layer. These rapidly-dissolving films were used to deliver
`
`pharmaceutically active agents and were typically made from water-soluble
`
`polymers. (Id.; Ex. 1024, Cassidy at 21-22.) Rapidly dissolving films were
`
`manufactured using conventional techniques, such as casting and drying. (Ex.
`
`1013,
`
`The Theory and Practice of Industrial Pharmacy, at 363.) The films were cut to
`
`the desired size that satisfied appropriate requirements and then packaged. (Ex.
`
`1023, Guo, at 227.) Chen discloses a cast film formulation formed from “a
`
`substantially homogenous preparation” for oral delivery of a pharmaceutical
`
`active. (Chen, Ex. 1005, at 4:24-32.) The components of the film were mixed to
`
`ensure the components were “uniformly dispersed . . . in the hydrocolloid.”
`
`(Chen, Ex.
`
`1005, at 17:6-11.)
`
`35.
`
`19.Hydrogel films were also known in the art. According to
`
`dissolution studies, hydrogel films were uniform when compared to one another.
`
`(Ex. 1024, Cassidy, at 25, Fig. 3.) Hydrogel films were also cast and contained
`
`pharmaceutical actives for oral delivery to achieve “rapid absorption.” (Ex. 1024,
`
`Cassidy, at 21- 22.) It was well-known in the art that dosage forms delivering
`
`pharmaceutical agents to patients needed to be uniform with respect to the
`--
`
`DRL - EXHIBIT 1003
`DRL015
`
`MonoSol2003-0026
`
`
`
`amount of drug found in each individual film dose. (See, e.g., Ex. 1023, Guo, at
`
`227-28.) Cassidy
`
`--
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`DRL - EXHIBIT 1003
`DRL015
`
`MonoSol2003-0027
`
`
`
`demonstrated, via dissolution studies, that the hydrogels exhibited uniform
`
`dissolution of the measured components. (Ex. 1024, Cassidy, at 25, Fig. 3.)
`
`36.
`
`20.A person of ordinary skill would have known to optimize
`
`uniformity of pharmaceutical actives in drug dosage forms, including films. No
`
`later than 1989, the Pharmakopoea Europae suggested that “uniformity of the
`
`weight of individually dosed drugs” should differ by no more than 5% across the
`
`dosage forms. (See, e.g., Ex. 1025, U.S. Pat. No. 4,849,246 (“the ’246 patent”), at
`
`1:63- 68.) And over the years, uniform films complying with this standard were
`
`developed. (See Ex. 1026,
`
`U.S. Pat. No. 5,393,528 (“the ’528 patent”), at 9:11-12 (the active agent “is evenly
`
`dispersed throughout the film matrix.”); Ex. 1028, Zerbe et al., U.S. Pat. No.
`
`5,629,003, at 1:54-57 (“homogeneous, water-soluble films intended for buccal
`
`administration of hormones”) (citing prior art to Zerbe).) The ‘528 patent, like
`
`others well-known in the art, included polymers. (Ex.1026,’528 patent, at
`
`Abstract, 10:66-11:3.) Uniform, cast films were also well known in the art. (See,
`
`e.g., Ex. 1028, U.S. Pat. No. 5,629,003, at 3:40, 5:51-53; Ex. 1029, Eur. Pat. No.
`
`EP0090560, at 4:15.) For example, in 1997 Guo disclosed film formulations
`
`containing pharmaceutical actives that could be manufactured using
`
`“conventional” techniques that “meet the requirements of the specific
`
`application.” (Ex. 1023, Guo at 227.)
`
`37.
`
`21.A person of ordinary skill would have known to use
`--
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`DRL - EXHIBIT 1003
`DRL016
`
`MonoSol2003-0028
`
`
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`taste-masking
`
`--
`
`DRL - EXHIBIT 1003
`DRL016
`
`MonoSol2003-0029
`
`
`
`agents, particularly when the pharmaceutical active of interest was known to be
`
`bitter or to have a bad taste. By 2001, many oral films included taste-masking
`
`agents. (Ex. 1004, Bess at 6:8-7:40.) These were also used by Chen “to achieve
`
`masking of taste for active agents that are bitter.” (Ex. 1005, Chen at 9:14-16.)
`
`Chen further disclosed that “encapsulation of the active agents may also be
`
`utilized to achieve masking of taste for active agents.” (Id. at 9:14-16.)
`
`III.Legal Standards
`22.In preparation for forming the opinions set forth in this declaration, I have been
`
`informed regarding the relevant legal principles. I have used my understanding of those
`
`principles in forming my opinions. My understanding of those principles is summarized
`
`below.
`
`23.I have been told that Teva bears the burden of proving invalidity by a
`
`preponderance of the evidence. I am informed that this preponderance of the evidence
`
`standard means that Teva must show invalidity is more probable than not. I have taken
`
`these principles into account when forming my opinions in this case.
`
`V.
`
`LEGAL STANDARDS
`
`38.
`
`I understand that a preponderance of evidence must be
`
`presented to render a patent claim invalid in this proceeding.
`
`39.
`
`I have been informed that the standard for obviousness is set
`
`out in 35 U.S.C. §103(a), the relevant version of which is quoted below:
`
`“A patent may not be obtained though the invention is not identically
`--
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`DRL - EXHIBIT 1003
`DRL017
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`MonoSol2003-0030
`
`
`
`disclosed or described as set forth in section 102 of this title, if the
`differences between the subject matter sought to be patented and the
`prior art are such that the subject matter as a whole would have been
`obvious at the time the invention was made to a person having
`ordinary skill in the art to which said subject matter pertains.
`Patentability shall not be negatived by the manner in which the
`invention was made.”
`
`35 U.S.C. § 103(a).
`
`40.
`
`I have been informed that in order for a patent claim to be
`
`considered obvious, at the time the invention was made, each and every
`
`limitation of the claim must be present within the prior art, or within the
`
`prior art in combination with the general knowledge held by a person of
`
`ordinary skills in the art, and that such a
`
`41.
`
`24.I have also been told that claims should be construed given their
`
`broadest reasonable interpretation in light of the specification from the
`
`perspective of a person of ordinary skill in the art.
`
`--
`
`DRL - EXHIBIT 1003
`DRL017
`
`MonoSol2003-0031
`
`
`
`person would have a reasonable expectation of success in combining these
`
`teachings to achieve the claimed invention. I also understand that the reason
`
`to select and combine features, the predictability of the results of doing so,
`
`and a reasonable expectation of success of doing so may be found in the
`
`teachings of the prior art themselves, in the nature of any need or problem in
`
`the field that was addressed by the patent, in the knowledge of persons of
`
`ordinary skill in the art at the time, as well as in common sense or the level of
`
`creativity exhibited by a POSA. There need not be an express or explicit
`
`suggestion to combine references. I understand the combination of familiar
`
`elements according to known methods is likely to be obvious when it does no
`
`more than yield predictable results.
`
`42.
`
`25.I am toldunderstand that the concept of patent obviousness
`
`involves fourof a claim is ultimately a legal conclusion based on underlying
`
`factual inquiries. I understand that the following factors are relevant to
`
`whether a claim is obvious: (1) the scope and content of the prior art; (2), the
`
`differences between the claimed invention and the prior art; (3) and the claims
`
`at issue, the level of ordinary skill in the art; and (4), and whatever objective
`
`evidence may be present.
`
`43.
`
`I understand that a claim may be obvious where it is the result of
`
`combining familiar elements according to known methods to achieve
`
`predictable results. The claim is obvious where a POSA would have been
`--
`
`DRL - EXHIBIT 1003
`DRL018
`
`MonoSol2003-0032
`
`
`
`motivated to combine the teachings of the prior art and would have had a
`
`reasonable expectation of success in doing so.
`
`--
`
`DRL - EXHIBIT 1003
`DRL018
`
`MonoSol2003-0033
`
`
`
`44.
`
`I understand that secondary considerations of non-obviousness. must
`
`be considered because such factors are probative of obviousness. These
`
`factors include unexpected results, commercial success, long felt but
`
`unresolved need, teaching away, and failure of others.
`
`26.I am also informed that when there is some recognized reason to solve a
`
`problem, and there are a finite number of identified, predictable and known solutions, a
`
`person of ordinary skill in the art has good reason to pursue the known options within his
`
`or her technical grasp. If such an approach leads to the expected success, it is likely not
`
`the product of innovation but of ordinary skill and common sense. In such a circumstance,
`
`when a patent simply arranges old elements with each performing its known function and
`
`yields no more than one would expect from such an arrangement, the combination is
`
`obvious.
`
`IV.Person of Ordinary Skill in the Art
`45.
`27.I have been informed by counsel that the obviousness analysis is to
`
`be conducted from the perspective of a person of ordinary skill in the art (a
`
`“person of ordinary skill”) at the time of the invention.relied upon this
`
`understanding of the applicable legal standards in reaching my opinions set
`
`forth in this declaration.
`
`28.I have also been informed by counsel that in defining a person of ordinary skill
`
`in the art the following factors may be considered: (1) the educational level of the
`
`inventor; (2) the type of problems encountered in the art;
`
`--
`
`DRL - EXHIBIT 1003
`DRL019
`
`MonoSol2003-0034
`
`
`
`(3)
`
`prior art solutions to those problems; (4) rapidity with which innovations are made; and
`
`(5) sophistication of the technology and educational level of active workers in the field.
`
`29.A person of ordinary skill in the art related to the ’514 patent would
`PERSON OF ORDINARY SKILL IN THE ART
`
`VI.
`
`46.
`
`It is my opinion that in the context of the ’514 patent, a person of
`
`ordinary skill in the art (“POSA”) would include a person who possesses a
`
`Masters Degree,Master’s or Ph.D. or their equivalent in pharmaceutics orin
`
`pharmaceutical sciences, formulation chemistry, or a related field , andplus a
`
`number of years of relevant experience in developing dosage forms for
`
`drugsdrug formulations.
`
`VII.
`
`V.The ’THE ‘514 PatentPATENT
`
`47.
`
`30.I have read the ’514 patent and the issued claims, entitled “Uniform
`
`Films
`
`for Rapid Dissolve Dosage Form
`
`Incorporating Taste-Masking
`
`Compositions.” The ’514 patent claims priority to several applications, listed on
`
`the face of the patent, the earliest of which is October 12, 2001, which I
`
`understand to be a provisional application. The ’514 patent issued December 10,
`
`2013, and names Robert K. Yang, Richard C. Fuisz, Garry L. Myers, and Joseph
`
`M. Fuisz as inventors.
`
`--
`
`DRL - EXHIBIT 1003
`DRL019
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`MonoSol2003-0035
`
`
`
`A.
`
`Priority Date of the’514 Patent
`
`48.
`
`31.The
`
`’514 patent was
`
`filed
`
`July 10, 2007, and
`
`is a
`
`continuation-in-part of application No. 10/768,809, filed on Jan. 30, 2004, now
`
`Pat. No. 7,357,891,
`
`and
`
`a
`
`continuation-in-part of
`
`application No.
`
`PCT/US02/32575, filed on Oct. 11, 2002, and a continuation-in-part of application
`
`No. 10/074,272, filed on Feb. 14, 2002, now Pat. No. 7,425,292; said application
`
`No. 10/768,809 is a continuation-in-part of application No. PCT/US02/32594,
`
`filed on Oct. 11, 2002, and a continuation-in- part of application No. 10/074,272;
`
`said application No. 10/768,809 is a continuation-in-part of application No.
`
`PCT/US02/32542, filed on Oct. 11, 2002, and a continuation-in-part of application
`
`No. 10/074,272, application No.11/775,484, which is a continuation-in-part of
`
`application No. 10/856,176, filed on May 28, 2004, now Pat. No. 7,666,337, and a
`
`continuation-in-part of application No. 10/768,809.
`
`B.
`
`Challenged Claims
`
`49.
`
`32.I understand that Teva is challengingThe challenged claims of
`
`the ‘514 patent include claims 1- 3, 9, 15, 62- 65, 69- 73, and 75 of the ’514
`
`patent. The ’514 patent includes two illustrative independent claims, claims 1
`
`and 62. Independent claim 1 recites:
`
`A drug delivery composition comprising:
`
`(i)
`
`a cast film comprising a flowable water-soluble or water
`
`swellable film-forming matrix comprising one or more
`--
`
`DRL - EXHIBIT 1003
`DRL020
`
`MonoSol2003-0036
`
`
`
`substantially
`
`--
`
`DRL - EXHIBIT 1003
`DRL020
`
`MonoSol2003-0037
`
`
`
`water soluble or water swellable polymers; and a desired amount of
`
`at least one active; wherein said matrix has a viscosity sufficient to
`
`aid in substantially maintaining non-self- aggregating uniformity of
`
`the active in the matrix;
`
`(ii)
`
`a particulate active substantially uniformly stationed in
`
`the matrix; and
`
`(iii)
`
`a taste-masking agent coated or intimately associated with said
`
`particulate to provide taste-masking of t
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