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
`Petitioners,
`
`v.
`
`RB PHARMACEUTICALS LTD.,
`
`INDIVIOR UK
`LIMITED, Patent Owner.
`
`U.S. PatentCase No.
`8,475,832Case IPR2016:
`Unassigned-XXXXX
`
`DECLARATION OF NANDITA DASMETIN ÇELIK, Ph.D. IN SUPPORT
`OF PETITION FOR
`INTER PARTES REVIEW OF U.S. PATENT NO. 8,475,832
`
`“SUBLINGUAL AND BUCCAL FILM COMPOSITIONS”
`
`DRL - EXHIBIT NO.
`1003
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`Dr. Reddy's Labs. v. Indivior UK Ltd, IPR2016-01113 - INDIVIOR EX. 2002 - 1/141
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`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`TEVA PHARMACEUTICALS USA, INC.,DR. REDDY’S
`LABORATORIES, LTD. AND DR. REDDY’S
`LABORATORIES, INC.,
`
`Petitioner
`Petitioners,
`
`v.
`
`RB PHARMACEUTICALS LTD.,
`
`INDIVIOR UK
`LIMITED, Patent Owner.
`
`U.S. PatentCase No.
`8,475,832Case IPR2016:
`Unassigned-XXXXX
`
`DECLARATION OF NANDITA DASMETIN ÇELIK, Ph.D. IN SUPPORT
`OF PETITION FOR
`INTER PARTES REVIEW OF U.S. PATENT NO. 8,475,832
`
`“SUBLINGUAL AND BUCCAL FILM COMPOSITIONS”
`
`DRL - EXHIBIT NO.
`1003
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`Dr. Reddy's Labs. v. Indivior UK Ltd, IPR2016-01113 - INDIVIOR EX. 2002 - 1/141
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`
`
`TABLE OF CONTENTS
`
`Page
`
`I.
`
`INTRODUCTION ...........................................................................................
`1
`II. QUALIFICATIONS........................................................................................
`1
`
`A.
`
`B.
`
`Education and Work Experience .......................................................... 3
`
`Professional Affiliations, Activities, and Awards ................................ 4
`
`C.
`
`Publications and Educational Involvement........................................... 5
`III. SCOPE OF THE WORK AND COMPENSATION ......................................
`6
`
`A.
`
`Bases for Opinion and Materials Considered ........................................ 7
`
`IV.
`
`SUMMARY OF OPINIONS ..........................................................................
`7
`
`V.
`
`PRIORITY DATE OF THE ’832 PATENT ...................................................
`7
`VI. LEGAL STANDARDS ................................................................................... 7
`VII. PERSON OF ORDINARY SKILL IN THE ART ........................................
`10
`
`VIII. THE ’832 PATENT....................................................................................... 10
`A.
`
`The Challenged Claims of the ’832 Patent .......................................... 10
`
`B.
`
`Prosecution History of the ’832 Patent................................................ 12
`IX. BACKGROUND AND TUTORIAL ............................................................
`21
`Therapeutic Range, Cmax, and AUC .................................................... 21
`
`A.
`
`B.
`
`Dosage Form Development ................................................................ 23
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`DECLARATION OF
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`
`
`C.
`
`D.
`
`E.
`
`F.
`
`Buprenorphine and Naloxone.............................................................. 25
`Suboxone® Sublingual Tablet.............................................................. 28
`Suboxone® Sublingual Film ................................................................ 30
`Development of Pharmaceutical Film Formulations ........................... 32
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`
`
`TABLE OF CONTENTS
`(Continued)
`
`G.
`
`Role of pH in Absorption of Buprenorphine and Naloxone................
`34
`
`X.
`
`THE CHALLENGED CLAIMS OF THE ’832 PATENT WOULD HAVE BEEN
`OBVIOUS.............................................................................. 36
`A.
`
`Scope and Content of the Prior Art .....................................................
`36
`
`1.
`
`Cassidy, et al., Controlled buccal delivery of
`buprenorphine, JOURNAL OF
`CONTROLLED RELEASE, 25 (1993) 21-29
`(“Cassidy”) (Ex. 1012) ............... 36
`
`2.
`
`U.S. Patent Publication 2005/0085440 (“Birch”) (Ex.
`1004)
`......................................................................................... 37
`3. WO2008/025791 (“Oksche”) (Ex. 1005).................................. 38
`Suboxone® Tablet 2002 Label (“Suboxone® 2002 Label”) (Ex. 1008)
`4.
`................................................................................. 38
`
`5.
`
`6.
`
`Tablet Summary Basis of Approval (“SBOA”) (Ex. 1009) ...... 38
`
`U.S. Patent No. 7,357,891 (“Yang”) (Ex. 1006) ....................... 39
`
`7. WO2008/040534 (“LabTec”) (Ex. 1007).................................. 39
`
`B.
`
`C.
`
`Claims 1-2, 4-7, and 9-10 Would Have Been Obvious Over LabTec in View of
`Yang, the Suboxone® 2002 Label, SBOA,
`Birch, and the Knowledge of a Person of Ordinary Skill .................... 40
`1.
`A Person of Ordinary Skill Would Have Been Motivated to Convert the
`Suboxone® Tablet Into Film Form .................... 40
`Claims 1-2, 4-7, and 9-10 Would Have Been Obvious Over Oksche in
`View of Yang, the Suboxone® 2002
`Label, SBOA, Birch ................................................................. 48
`
`2.
`
`Claims 3 and 11-12 Are Obvious In Further View Of The ’055
`Publication........................................................................................... 53
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`XI. CONCLUSION ............................................................................................. 54
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`I, Metin Çelik, Ph.D. declare as follows:
`
`I.
`
`IntroductionINTRODUCTION
`
`1. My name is Nandita DasMetin Çelik. I have been retained by counsel
`
`for Petitioner Teva Pharmaceuticals USA, Inc. (“Teva”). I understand that
`
`Teva petitioned for inter partes review of U.S. Patent No. 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 8,475,832 (“the “’832 patent”), which is owned by RB Pharmaceuticals
`
`Ltd. (“Patent Owner‘832 Patent”). I further understand that TevaDr. Reddy’s
`
`requests that the United States Patent and Trademark Office (“USPTO”) cancel
`
`certain claims of the ’832 patent as unpatentable. I submit this expert declaration,
`
`which addresses and supports Teva’s petition.
`
`which addresses and supports the petition of Dr. Reddy’s.
`
`II.
`
`Personal Background and Expert QualificationsQUALIFICATIONS
`
`a. Experience and Prior Testimony
`
`2. Currently, I am an Associate Professor of Pharmaceutics at
`
`Butler University with over 15 years of experience teaching pharmaceutical
`
`sciences. I have been on the faculty at Butler University since 2004 with a
`
`full-time campus- based tenure-track faculty position since 2005. I was
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`granted tenure and promoted to Associate Professor in Spring 2012. Prior to
`
`my time at Butler University, I was an Assistant Professor of Pharmaceutics at
`
`Idaho State University, previous to which I taught as an Adjunct Professor
`
`at Nova Southeastern University while working full time as a licensed
`
`pharmacist in the state of Florida. A copy of my curriculum vitae and list of
`
`publications is attached as Exhibit A. I 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 received a B.Pharm. in Pharmacy from Banaras Hindu Since
`
`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.
`
`India in 1988, achieving first rank among my classmates.
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`4.
`
`I received an M.Pharm. in Pharmaceutics from Banaras Hindu
`
`Over the past thirty years, working in industry, academia, and as a 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”).
`
`University in 1990. My research focused on controlled release dosage forms.
`I received a Ph.D. in Pharmaceutical Sciences from the University
`5.
`
`of Pittsburgh in 1995. My research focused on the kinetics of solid-state
`
`microcalorimetry. 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.
`
`From 1993-1995, I completed my doctoral research work as a
`
`graduate scholar with SmithKline Beecham Pharmaceuticals, studying
`
`microcalorimetry under the mentorship of Dr. Theodore D. Sokoloski, Ph.D.
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`
`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 (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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`
`
`A.
`
`Education and Work Experience
`
`7. From 1995-1998, I worked as a commercial pharmacist, managing a
`community pharmacy.I earned my B.Sc. (Hons.) degree in Pharmacy from
`Hacettepe
`
`University in Turkey in 1979.
`
`8. My business address is College of Pharmacy & Health Sciences,
`
`Butler University, 4600 Sunset Avenue, Indianapolis, IN 46208-3485. 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.
`
`Among the numerous research grants I have received, from
`
`August 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.
`
`2002 through July 2006, I conducted a study on the use of mucoadhesive
`
`buprenorphine in opioid addiction therapy for the National Institute of Health’s
`
`National Institute on Drug Abuse.
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`10.
`
`In 2004, I published an article on the development of
`
`mucoadhesive dosage forms of buprenorphine for sublingual delivery in Drug
`
`Delivery – The Journal of Delivery and Targeting of Therapeutic Agents,
`
`Volume 11 (2004). In 1986, I joined Smith Kline & French Laboratories
`
`(presently known as GlaxoSmithKline) in Swedeland, Pennsylvania, where I
`
`developed and established the first state-of-the-art Compaction Simulator
`
`System in the Western hemisphere.
`
`11.
`
`I have also researched, as part of my work during my time at Idaho
`
`State University, mucoadhesive properties of polymers used in sublingual
`
`drug delivery. 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
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`courses included Drug Delivery, Problems in Pharmaceutics, and Pharmaceutical
`
`Processes and Equipment.
`
`12.
`
`I also co-authored a paper regarding drugs used in the treatment
`
`of addiction for the Indian Journal of Pharmacy Practice, Volume 5, Issue 4
`
`(2012). 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.
`
`I have authored or co-authored over 70 articles, abstracts, papers
`
`and book chapters and am a named inventor on one domestic patent. I have
`
`also appeared at six conferences on a topic areas of present interest,
`
`including mucoadhesive sublingual delivery systems for buprenorphine.
`
`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.
`
`14.
`
`Professional Affiliations, Activities, and Awards
`
`I am or have been a member of the following professional
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`14.
`
`I am a member of various professional societies, includingorganizations:
`
`the American Association of Pharmaceutical Scientists and(AAPS), the New
`
`Jersey Pharmaceutical Association of Science and Technology (NJPhAST), the
`
`American Association of Colleges of Pharmacy. I am also a peer reviewer for five
`
`scientific and medical journals (AACP), and the Ankara Chamber of
`
`Pharmacists (ACP).
`
`b. Bases for Opinion and Materials Considered
`15. Exhibit 10026 includes a list of the materials I considered, in addition
`
`to my experience, education, and training, in providing the opinions contained
`
`herein. I 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
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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.c.
`Scope of Work
`In 1991, 1993, and 1994, I received the Faculty Academic Service
`
`16.
`
`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.
`
`19.
`
`Publications and Educational Involvement
`
`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
`
`the International Journal of Pharmaceutics. In addition, I have made over 200
`
`presentations at
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`industry, academic, national and international meetings, and conferences,
`
`most of which by invitation.
`
`21. Attached to this Declaration as Appendix A is a copy of my
`
`Curriculum Vitae which details my professional experience and expertise in
`
`relation to the fields of pharmaceutical formulation and process development.
`
`III.
`
`SCOPE OF THE WORK AND COMPENSATION
`
`22.
`
`I have been engaged by Dr. Reddy’s to provide my opinions relating
`
`to certain claims of U.S. Patent 8,475,832 (“the ‘832 Patent”).
`
`23. 16. I have been retained by Teva as a technical expert in this
`
`matterasked to provide variousmy opinions regarding the ’832 patent. I receive
`
`$400 per hour for my services and $500 per hour for deposition testimony. No
`
`part of my compensation(a) the person of ordinary skill in that art (“POSA”)
`
`relevant to the ‘832 patent and (b) whether certain references render the
`
`asserted claims obvious to the POSA as of August 7,
`
`2009.
`
`24.
`
`I am being compensated for my time 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. Reddy’s. I do not have
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`any current or past affiliation with Indivior UK Limited, formally known as RB
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`Pharmaceuticals Limited, or any of the named inventors on the ’832 patent.
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`III.
`
`Summary of Opinions
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`A.
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`Bases for Opinion and Materials Considered
`
`25. Exhibit 1026 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. 17. As explained in detail in Section VIII, it is my opinion that all of the
`
`challenged claims (1-7, 9-12) of the ’832 patent1 would have been obvious in light of
`
`the LabTec reference, the Oksche reference, the 2002 Suboxone® Label, and other
`
`prior art, which would have collectively taught and motivated a person of ordinary
`
`skill in the artPOSA to make and use the same compositions and methods that are
`
`claimed in the ’832 patent.
`
`are claimed in the ’832 patent.
`
`V.
`
`IV. Priority Date of the ’832 PatentPRIORITY DATE OF THE ’832 PATENT
`
`27. 18. I am informed and understand that prior art is evaluated based on
`
`the priority date attributed to the patent under review. Further, I understand that
`
`Patent Owner claims the ’832 patent is entitled to priority date of August 7, 2009. I
`
`understand that patents and printed publications published prior to August 7, 2009
`
`are available as prior art to the ’832 in this proceeding.
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`Legal Standards
`V.
`are available as prior art to the ’832 in this proceeding.
`
`VI. LEGAL STANDARDS
`
`28. 19. I understand that a preponderance of evidence must be
`
`presented to render a patent claim invalid in this proceeding.
`
`
`1 It is my understanding that claims 15-19 have been found invalid in IPR2014- 00325.
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`20. I have been informed that the standard for obviousness is set out
`
`29.
`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
`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).
`
`21.
`
`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
`
`30.
`
`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 skillsskill in the art, and that such
`
`a 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
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`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 person
`
`of ordinary skill in the art. There need not be an express or explicit suggestion to
`
`combine references. I understand the combination of familiar
`
`the time, as well as in common sense or the level of creativity exhibited by a POSA.
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`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.
`
`31.
`
`22. I understand that the obviousness of 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: the scope and content of the prior
`
`art, the differences between the prior art and the claims at issue, the level of ordinary
`
`skill in the art, and whatever objective evidence may be present.
`
`ordinary skill in the art, and whatever objective evidence may be present.
`
`32.
`
`23. 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 person of ordinary skill in the art would
`
`havePOSA would have been motivated to combine the teachings of the prior art
`
`and would have had a reasonable expectation of success in doing so.
`
`been motivated to combine the teachings of the prior art and would have had a reasonable
`
`expectation of success in doing so.
`
`33.
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`24. I understand that secondary considerations of non-obviousness must
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`be considered because such factors are probative of obviousness. These factors
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`include unexpected results, commercial success, long felt but unresolved need,
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`teaching away, and failure of others.
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`34.
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`25. I have relied upon this understanding of the applicable legal
`
`standards in reaching my opinions set forth in this declaration.
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`VI.
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`Person of Ordinary Skill in the Art
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`VII.
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`PERSON OF ORDINARY SKILL IN THE ART
`
`35.26. It is In my opinion that in the context of the ’832 patent, a person of
`
`ordinary skill in the art would include a person who possesses a Master’s or
`
`Ph.D. in, the POSA as of August 2009 would have a degree in the
`
`pharmaceutical sciences, formulation chemistry, or a related filed, plus a number
`
`of years of relevant experience in developing drug formulations.field, and
`
`several years of practical experience in pharmaceutical formulation and
`
`processing, namely, a Ph.D. and 2-3 years of such experience; or a master’s
`
`degree and 4-5 years of such experience; or
`
`a bachelor’s degree and 6-7 years of such experience.
`
`VIII.
`
`VII. TheTHE ’832 PatentPATENT
`
`A.
`
`The Challenged Claims of the ’832 Patent
`
`36.27. The challenged claims of the ’832 patent are directed to a composition
`
`(claims 1-7), and a method of treating narcotic dependence of a user (claims 9-12).
`
`More particularly, the challenged claims recite:
`
`1. A film dosage composition comprising:
`a. A polymeric carrier matrix;
`b. A therapeutically effective amount of buprenorphine or a
`pharmaceutically acceptable salt thereof;
`c. A therapeutically effective amount of naloxone or a
`pharmaceutically acceptable salt thereof; and
`d. A buffer in an amount to provide a local pH for said composition of
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`a value sufficient to optimize absorption of said buprenorphine,
`wherein said local pH is from about 3 to about 3.5 in the presence of
`saliva.
`2. The composition of claim 1, wherein said film dosage
`composition provides a bioequivalent absorption of buprenorphine to
`that of a tablet having an equivalent amount of buprenorphine or a
`pharmaceutically acceptable salt thereof.
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`that of a tablet having an equivalent amount of buprenorphine or a
`pharmaceutically acceptable salt thereof.
`3. The composition of claim 1, wherein said polymeric carrier
`matrix comprises at least one polymer in an amount of at least 25% by
`weight of said composition.
`4. The composition of claim 1, wherein said buffer is present in an
`amount of from about 2:1 to about 1:5 by weight of buffer to
`buprenorphine.
`5. The composition of claim 1, wherein said polymeric carrier
`matrix comprises at least one self-supporting film forming polymer.
`6. The
`film dosage composition of claim 1, wherein said
`buprenorphine is present in an amount of from about 2 mg to about 16
`mg per dosage.
`7. The film dosage composition of claim 1, wherein said buffer
`comprises sodium citrate, citric acid, and combinations thereof.
`9. A method of treating narcotic dependence of a user, comprising
`the steps of:
`a.
`providing a composition comprising:
`i.
`a polymeric carrier matrix;
`ii.
`a therapeutically effective amount of buprenorphine or a
`pharmaceutically acceptable salt thereof;
`iii.
`a therapeutically effective amount of naloxone or a
`pharmaceutically acceptable salt thereof; and
`iv. A buffer in an amount to provide a local pH of about 3 to about
`3.5 for said composition of a value sufficient to optimize absorption of
`said buprenorphine and also sufficient to inhibit absorption of said
`naloxone; and
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`administering said composition to the oral cavity of a user.
`b.
`10. The composition of claim 9, wherein said method provides a
`bioequivalent absorption of buprenorphine to that of a tablet having an
`equivalent amount of buprenorphine or a pharmaceutically acceptable
`salt thereof.
`11. The method of claim 9, wherein said film dosage composition is
`administered to the user through buccal administration, sublingual
`administration, and combinations thereof.
`12. The method of claim 9, wherein said film dosage composition
`remains in the oral cavity of the user for a period of at least 1 minute. B.
`Prosecution History of the ’832 Patent
`
`B.
`37.
`
`Prosecution History of the ’832 Patent
`28. I have reviewed the prosecution history of the ’832 patent. The
`
`application leading to the ’832 patent (U.S. Patent Application No. 12/537,571) was
`
`filed on August 7, 2009 and lists Garry L. Myers, Samuel D. Hilbert, Bill J. Boone,
`
`B. Arlie Bogue, Pradeep Sanghvi, and Madhusudan Hariharan as inventors. I also
`
`understand that the ’832 patent was assigned to RB Pharmaceuticals Limited.2 (’832
`
`patent, Ex. 1001.) As filed, the ’571 application included 31 claims. (U.S.
`
`Boone, B. Arlie Bogue, Pradeep Sanghvi, and Madhusudan Hariharan as inventors.
`
`I also understand that the ’832 patent was assigned to RB Pharmaceuticals Limited. (’832
`
`patent, Ex. 1001.) As filed, the ’571 application included 31 claims. (U.S. Patent App. No.
`
`12/537,571, Ex. 1002 at 33-36 ( the “’571 application”).) Claims 1, 11, 15, 17, 24, 26, and 27
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`were independent claims. (Id. at 33-36.) None of these independent claims recited any pH
`
`ranges. (Id. at 33-36.)
`
`2 I have been informed that Indivior UK Limited is the current assignee of the
`‘832 patent.
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`38.
`
`29. On August 31, 2011, the Examiner issued a non-final Office Action
`
`rejecting claims 1, 4, 5, 7-10, 15, 17, and 20-24 as anticipated by the Oksche, et al.,
`
`reference (US2010/0087470). (8/31/11 Office Action (’571 Application), Ex. 1002 at
`
`2.) The Examiner pointed to certain embodiments in the Oksche reference that
`
`disclosed all of the elements of the rejected claims. (Id. at 2-3.)
`
`39.
`
`30. In addition, the Examiner rejected claims 1-31 as obvious, noting
`
`that it would have been obvious to a person of ordinary skillPOSA to modify the
`
`teachings of Oksche to identify the optimal pH range “in an effort to identify
`
`formulations that would provide optimal absorption of both agonist and antagonist.”
`
`(Id. at 5.) Oksche disclosed “buprenorphine/naloxone formulations [that] may
`
`comprise the citric acid as a pH modifier.” (Id. at 4.) And the Examiner explained that
`
`because the general conditions of the claimed invention were known in the prior art,
`
`identification of the optimal pH range “appears to be a matter of routine
`
`experimentation.” (Id. at 5.)
`
`40.
`
`31. The Examiner concluded that it was inconsequential that Oksche
`
`did “not teach formulations [of] buprenorphine and naloxone, where the buffer
`
`is present in an amount sufficient to inhibit the absorption of naloxone.” (Id. at
`
`4.) The Examiner also stated that it did not matter that Oksche did not “teach the
`
`specific range of pH recited in the instant claims.” (Id. at 4.)
`
`41. On February 29, 2012, Applicants responded to the Office Action
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`and amended the claims “to recite a particular local pH value and/or to recite that
`
`the
`
`On February 29, 2012, Applicants responded to the Office Action and amended the
`32.
`claims “to recite a particular local pH value and/or to recite that the
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`buffer optimizes absorption of buprenorphine while also inhibiting absorption of
`
`the naloxone.” (2/29/12 Amendment and Response (’571 Application), Ex. 1002 at
`
`7.)
`
`In particular, claim 1 was amended to include a “local pH” of “from about 2 to
`
`about 3.5 in the presence of saliva.” (Id. at 2.) Claim 17 (which issued as
`
`independent claim 9) was also amended to include a “local pH” of “about 2 to about
`
`3.5.” (Id. at 4.)
`
`3.5.” (Id. at 4.)
`
`42.
`
`33. In addition to amending the claims, Applicants described the
`
`invention and acknowledged that the simultaneous delivery of buprenorphine and
`
`naloxone was not novel; it had been previously known in the form of the
`
`Suboxone® tablet. (Id. at 7.) The alleged invention was intended to provide a
`
`maximum blood concentration (Cmax) that is 80 to 125% of the level provided by a
`
`Suboxone® tablet at the same dosage levels of buprenorphine and naloxone. (Id. at
`
`7.) In order to
`
`7.)
`
`In order to achieve this desired result, Applicants “discovered that the
`
`film product should include a buffer that provides a specific buffer capacity to
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