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, Patent Owner.
`
`U.S. Patent No. 8,017,150
`
`Case No. IPR2016: Unassigned-XXXXX
`
`DECLARATION OF NANDITA DAS, Ph.D.RUSSELL J. MUMPER,
`Ph.D. IN SUPPORT OF PETITION FOR INTER PARTES REVIEW
`OF U.S. PATENT NO. 8,017,150
`
`“POLYETHYLENE OXIDE-BASED FILMS AND DRUG DELIVERY
`SYSTEMS MADE THEREFROM”
`
`DRL - EXHIBIT NO.
`1003 Page 1 of 56
`
`MonoSol2003-0001
`
`Dr. Reddys v. MonoSol
`IPR2016-01112
`
`
`
`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, Patent Owner.
`
`U.S. Patent No. 8,017,150
`
`Case No. IPR2016: Unassigned-XXXXX
`
`DECLARATION OF NANDITA DAS, Ph.D.RUSSELL J. MUMPER,
`Ph.D. IN SUPPORT OF PETITION FOR INTER PARTES REVIEW
`OF U.S. PATENT NO. 8,017,150
`
`“POLYETHYLENE OXIDE-BASED FILMS AND DRUG DELIVERY
`SYSTEMS MADE THEREFROM”
`
`DRL - EXHIBIT NO.
`1003 Page 1 of 56
`
`MonoSol2003-0001
`
`Dr. Reddys v. MonoSol
`IPR2016-01112
`
`
`
`TABLE OF CONTENTS
`
`Page
`QUALIFICATIONS AND BACKGROUND ................................
`I.
`Education and Experience; Prior Testimony...................................1
`
`Basis for Opinion and Materials Considered ...................................9
`
`A.
`
`B.
`
`Scope of Work......................................................................................9
`C.
`SUMMARY OF OPINIONS ......................................................................10
`
`II.
`
`III. LEGAL STANDARDS................................................................................14
`
`IV. PERSON OF ORDINARY SKILL IN THE ART....................................16
`V.
`THE ’150 PATENT .....................................................................................16
`
`A.
`
`B.
`
`Relevant Prosecution History of the ’150 Patent ...........................20
`
`Priority Date of The ’150 Patent......................................................20
`
`VI. BACKGROUND AND TECHNOLOGY TUTORIAL ...........................26
`
`A. Mucosally-Adhesive Drug Delivery Systems..................................26
`B.
`Polymers.............................................................................................30
`
`C. Molecular Weight of Polymers ........................................................31
`
`D.
`
`Oral Films as Delivery Systems .......................................................35
`
`1.
`
`Common Components of Oral Films ....................................36
`
`Determining the Ratios of Polymer Film Components.......38
`2.
`VII. SCOPE AND CONTENT OF THE PRIOR ART REFERENCES........42
`
`A.
`
`Scope and Content Of The Prior Art As Of October 12, 2001 .....43
`
`WO2000/42992 (“Chen”) (Ex. 1021) ...............................................43
`
`U.S. Application Pub. No. 2002/0147201 (“Chen II”)
`-i-
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`DRL - EXHIBIT 1003
`DRL2
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`MonoSol2003-0002
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`
`
`(Ex. 1049) .................................................................................47
`U.S. Patent No. 4,713,243 (“Schiraldi”) (Ex. 1004)........................48
`
`U.S. Patent No. 6,322,811 (“Verma”) (Ex. 1005)............................50
`
`U.S. Patent No. 5,656,296 (“Khan”) ................................................51
`
`B.
`
`Summary of the Scope and Content of the Prior Art....................51
`
`1. Mucosally-adhesive water-soluble film products.................51
`PEO in combination with cellulosic polymers6 ...................52
`Films containing PEOs of varying molecular weights ........52
`
`2.
`
`3.
`
`C.
`
`Scope And Content of the Prior Art as of April 22, 2008..............53
`
`U.S. Patent App. No. 2005/0037055 (“Yang”) (Ex. 1006)..............53
`
`VIII. INVALIDITY OF THE ’150 PATENT.....................................................54
`A.
`Claims 1, 3-5, 7-10, 12-14, and 15-18 are Obvious over Chen
`in View of Schiraldi, Claims 6 and 14 are Obvious over Chen
`in
`View of Schiraldi and Additionally in View of Chen II.................54
`
`B.
`
`Claims 1, 4-5, 8, 10, 13-14, and 17 Are Obvious Over Schiraldi
`in View of Verma...............................................................................59
`
`1.
`
`Claims 4 and 13 are Obvious Over Schiraldi in View of
`Verma.......................................................................................64
`
`2.
`
`Claims 5, 8, 14 and 17 are Obvious Over Schiraldi in
`View of Verma.........................................................................64
`Claims 6-7, 9, 15-16, and 18 Are Obvious Over Schiraldi in
`View of Verma and Khan.................................................................65
`
`C.
`
`1.
`
`2.
`
`Claims 6 and 15 are Obvious Over Schiraldi in View of
`Verma and Khan.....................................................................65
`
`Claims 7 and 16 are Obvious Over Schiraldi in View of
`Verma and Khan.....................................................................65
`
`-ii-
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`DRL - EXHIBIT 1003
`DRL003
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`MonoSol2003-0003
`
`
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`3.
`
`Claims 9 and 18 are Obvious Over Schiraldi in View of
`Verma and Khan.....................................................................65
`The Challenged Claims Would Have Been Obvious As Of April
`22, 2008 Over Yang...........................................................................65
`
`D.
`
`1.
`
`Claims 4-9 and 13-18 Would Have Been Obvious as of
`April 22, 2008 Over Yang.......................................................66
`IX. CONCLUSION............................................................................................67
`
`-iii-
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`DRL - EXHIBIT 1003
`DRL004
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`MonoSol2003-0004
`
`
`
`1. My name is Nandita DasRussell J. Mumper. I have been retained by
`
`counsel for Petitioner Teva Pharmaceuticals USA, Inc. (“Teva”). Dr. Reddy’s
`
`Laboratories, Inc. and Dr. Reddy’s Laboratories, Ltd. (collectively – “Dr.
`
`Reddy’s”).
`
`I understand that TevaDr. Reddy’s is petitioning
`
`for inter partes review of U.S. Patent No. 8,017,150 (the “’150 patent”), which is
`
`owned by MonoSol RX, LLC.
`
`I further understand that TevaDr. Reddy’s will
`
`request that the United States Patent and Trademark Office (“USPTO”) cancel
`
`certain claims of the ’150 patent as unpatentable.
`
`I submit this expert
`
`declaration, which addresses and supports TevaDr. Reddy’s petition.
`
`I.Qualifications and Background
`I.
`QUALIFICATIONS AND BACKGROUND
`
`A.
`
`A.Education and Experience; Prior Testimony
`
`2.
`
`Currently, I am an Associate Professor of Pharmaceutics at Butlerthe
`
`Vice Provost for Academic Affairs for University of Georgia at Athens, with
`
`over 15more than 25 years of combined research, product development and
`
`teaching experience teachingin the pharmaceutical sciences. I have been on the
`
`faculty at Butler University of Georgia in Athens, Georgia since 2004 with a
`
`full-time campus- based tenure-track faculty position since 2005. I was granted
`
`tenure and promoted to Associate Professor in Spring 2012.2014, where I hold full
`
`Professor positions (with tenure) in both the College of Pharmacy and the
`
`College of Engineering. Prior to my timeemployment at Butler University, I was
`-1-
`
`DRL - EXHIBIT 1003
`DRL005
`
`MonoSol2003-0005
`
`
`
`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 Ex. 1047.the University of
`
`Georgia, I was the John A. McNeill Distinguished Professor in the Division of
`
`Molecular Pharmaceutics at the University of North Carolina’s (“UNC”)
`
`Eshelman School of Pharmacy in Chapel Hill, NC. At UNC, I was also the
`
`founding Director of the Center for Nanotechnology in Drug Delivery and
`
`Co-Director of UNC’s Institute
`
`-2-
`
`DRL - EXHIBIT 1003
`DRL005
`
`MonoSol2003-0006
`
`
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`for Nanomedicine. Prior to that, I had been Vice Chair of the Department of Pharmaceutical
`
`Sciences at the University of Kentucky’s College of Pharmacy in Lexington, KY, where I
`
`also last served as an Associate Professor after receiving early tenure in 2003. For more
`
`than a decade at the University of Kentucky and the University of North Carolina at
`
`Chapel Hill, I taught a required first year course to pharmacy students pertaining to
`
`pharmaceutics and pharmaceutical dosage forms. This course covered a wide range of
`
`dosage forms by all different routes of administration including topical, injectable, oral,
`
`nasal, and buccal, among others. Prior to my time at University of Kentucky, I worked in
`
`industry, first at Burroughs Wellcome, Co. (now GlaxoSmithKline), then at Gene
`
`Medicine, Inc. (which became Valentis, Inc.), and at the ViroTex Corporation. I have
`
`also founded pharmaceutical start-up companies and served on the Board of Directors
`
`for angel investor and venture capital-backed companies. A copy of my curriculum vitae
`
`and list of publications is attached as Ex. A and filed as Ex. 1047.3.I received a B.Pharm. in
`
`Pharmacy from Banaras Hindu University in India in 1988, achieving first rank among my
`
`classmates.
`
`4.I received an M.Pharm. in Pharmaceutics from Banaras Hindu University in 1990. My
`
`research focused on controlled release dosage forms.
`
`5.I received a Ph.D. in Pharmaceutical Sciences from the University of Pittsburgh in 1995. My
`
`research focused on the kinetics of solid-state microcalorimetry.
`
`6.From 1993-1995, I completed my doctoral research work as a graduate scholar with SmithKline
`
`-2-
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`DRL - EXHIBIT NO.
`1003 Page 2 of 56
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`MonoSol2003-0007
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`
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`Beecham Pharmaceuticals, studying microcalorimetry under the mentorship of Dr.
`
`Theodore D. Sokoloski, Ph.D.
`
`7.From 1995-1998, I worked as a commercial pharmacist, managing a community pharmacy.
`
`3.
`
`8.My business address is College of Pharmacy & Health Sciences,
`
`Butler University, 4600 Sunset Avenue, Indianapolis, IN
`
`46208-3485.University of Georgia, 204 Administration Building, 220 South
`
`Jackson Street, Athens, GA 30602.
`
`4. My academic research programs have focused primarily in
`
`nanotechnology-based drug delivery and cell targeting, mucoadhesive gels and
`
`films for transmucosal drug delivery, and anti-cancer and anti-inflammatory
`
`properties of berries and berry extracts. From 1999 to the present, I received
`
`many
`
`-3-
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`DRL - EXHIBIT NO.
`1003 Page 3 of 56
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`MonoSol2003-0008
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`
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`grants and contracts to support my research programs including from the
`
`National Institutes of Health and National Science Foundation, foundations,
`
`and many companies. In total, I received 42 grants or contracts from Federal
`
`funding agencies or foundations and 41 from pharmaceutical and
`
`biotechnologies companies.
`
`5.
`
`From 1992 until 1999, I worked in the pharmaceutical and
`
`biotechnology industries for three companies: Burroughs Wellcome Co.,
`
`GeneMedicine, and ViroTex Corporation. During these seven years, I was
`
`involved in various aspects of the creation of drug delivery systems including
`
`immediate and sustained oral solid dosage forms, gene delivery systems, and
`
`topical, vaginal and buccal dosage forms. I directed groups of scientists and
`
`efforts to transfer the discoveries into human clinical trials. While at ViroTex,
`
`I served as Director of Product Development and designed, optimized, and
`
`scaled-up drug delivery systems for topical (skin) and mucosal (buccal)
`
`delivery. Delivery systems were primarily polymer-based formulations applied
`
`as films, gels, pump sprays, or aerosols. At ViroTex, I led research effort on the
`
`application of ViroTex’s BEMA (BioErodible MucoAdhesive) delivery
`
`technology for buccal delivery and mucosal vaccines.
`
`6.
`
`I received a B.A. Chemistry from University of Kentucky,
`
`Lexington, Kentucky in 1988 with High Distinction and Departmental
`
`-3-
`
`DRL - EXHIBIT 1003
`DRL007
`
`MonoSol2003-0009
`
`
`
`Honors.
`
`-4-
`
`DRL - EXHIBIT 1003
`DRL007
`
`MonoSol2003-0010
`
`
`
`7.
`
`I obtained a Ph.D. in Pharmaceutical Sciences
`
`(Pharmaceutics/Drug Delivery) from the University of Kentucky College of
`
`Pharmacy in 1991.
`
`8.
`
`After receiving my Ph.D., I performed postdoctoral research
`
`from 1991-1992 under the direction of Professor Allan S. Hoffman and
`
`University of Washington, Seattle, Center for Bioengineering. My
`
`postdoctoral research was in the area of protein drug delivery.
`
`9.
`
`Among the numerous research grants I have received, from August
`
`2002 through July 2006, I conducted a study on the use of mucadhesive
`
`buprenorphine in opioid addiction therapy for the National Institute of Health’s
`
`National Institute on Drug Abuse.In addition to my industry experience in
`
`research and development, I have directly co-founded three companies that
`
`licensed technologies developed in my university laboratories. These
`
`companies worked to develop novel medical, drug and health products.
`
`NanoMed Pharmaceuticals Inc., which I co-founded in 2000, developed
`
`nanoparticle-based advanced drug delivery systems to diagnose and treat
`
`disease. I was a co-inventor on all of the founding technology of NanoMed
`
`Pharmaceuticals which includes nanoparticle manufacturing processes,
`
`mucoadhesive thin-films, and topical film-forming gels. Then, in 2004, I co-
`
`founded Four Tigers, LLC. Four Tigers develops a pipeline of products
`
`-4-
`
`DRL - EXHIBIT 1003
`DRL008
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`MonoSol2003-0011
`
`
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`utilizing disease-preventative and therapeutic properties of blackberries
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`including chewing gums, topical products, and mucoadhesive thin-films. In
`
`2009, I co-founded Capture Pharmaceuticals LLC, which develops prodrugs
`
`of chelating agents to treat people contaminated with radioisotopes in the
`
`event of a nuclear explosion or radioactive “dirty bomb,” or people suffering
`
`from toxicity due to the use of
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`-5-
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`DRL - EXHIBIT 1003
`DRL008
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`MonoSol2003-0012
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`
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`gadolinium-based MRI contrast agents.
`
`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).While
`
`serving as the John A. McNeill Distinguished Professor at the University of
`
`North Carolina, Chapel Hill a major focus of my research was mucoadhesive
`
`gels, thin-films, and intravaginal rings for the transmucosal delivery of drugs,
`
`vaccines and microbicides.
`
`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.
`
`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).
`
`11.
`
`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 6 conferences on topic areas of present interest, including
`
`mucoadhesive sublingual delivery systems for buprenorphine.more than 300
`
`scientific publications, including peer reviewed journal articles and abstracts
`
`on various aspects of pharmaceutics and advanced drug delivery systems for
`
`the delivery of small drugs, peptides and proteins, DNA, and vaccines. A
`
`complete list of my publications and other activities can be found in my
`
`-5-
`
`DRL - EXHIBIT 1003
`DRL009
`
`MonoSol2003-0013
`
`
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`curriculum vitae dated June 2016, attached as Ex. A and filed as Ex. 1047.
`
`12.
`
`I have published a number of peer reviewed papers on
`
`transmucosal delivery of drugs and mucoadhesive systems. For example, I
`
`co-authored a paper titled “Transmucosal Delivery of Testosterone in
`
`Rabbits using Novel Bi-Lay Mucoadhesive Wax-Film Composite Disks,” by
`
`Jay, S. et al. published in J. Pharm. Sci.(2002) 91(9): 2016-2025. I was also
`
`coauthor of the article “Formulation and In-Vitro and In-Vivo Evaluation of
`
`a Mucoadhesive Gel Containing Freeze Dried Black Raspberries: Implication
`
`for Oral Cancer Chemoprevention,” by Mallery, S.R. published in Pharm.
`
`Res. (2007) 24(4): 728- 737.
`
`-6-
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`DRL - EXHIBIT 1003
`DRL009
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`MonoSol2003-0014
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`
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`13.
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`I am the inventor or co-inventor of at least 49 U.S. and foreign
`
`patents and patent applications. I have prepared patent applications submitted
`
`to the United States Patent Office as well as patent offices overseas. I have also
`
`been active in responding to Office actions. These patents have included the
`
`invention of thin-film and film-forming gel technologies specifically designed
`
`for the trans(mucosal) delivery of drugs and vaccines.
`
`14.
`
`I am a member of various professional societies, including the
`
`American Association of Pharmaceutical Scientists and the American
`
`Association of Colleges of Pharmacy. I am also a peer reviewer for five scientific
`
`and medical journals.also co-inventor of patents for mucoadhesive drug
`
`delivery systems. For example, I am a co-inventor of two U.S. patents both
`
`titled “pH- Sensitive Mucoadhesive Film-form Gels and Wax-film
`
`Composites Suitable for Topical and Mucosal Delivery of Molecules,” U.S.
`
`Patent Nos. 8,865,150 and 7,803,392.
`
`15.
`
`Since 1999, I have served on more than 25 scientific review panels
`
`for the National Institutes of Health, including serving as Chair of a Study
`
`Section.
`
`16. Over the past 15 years I have been routinely asked to review
`
`manuscripts submitted to almost thirty different scientific journals with
`
`most pertaining to advanced drug delivery systems. Some of these journals
`
`include: Advanced Drug Delivery Reviews, Biomaterials, Critical Reviews in
`
`DRL - EXHIBIT 1003
`DRL10
`
`MonoSol2003-0015
`
`
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`Therapeutic Drug Carrier Systems, European Journal of Pharmaceutics and
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`Biopharmaceutics, Expert Opinion in Drug Delivery, International Journal of
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`Nanomedicine, International Journal of Pharmaceutics, Journal of Applied
`
`Polymer Science, Journal of Controlled Release, Journal of Dispersion Science
`
`and Technology, Journal of Drug Targeting, Journal of Pharmaceutical
`
`Sciences, and Molecular Pharmaceutics, among others.
`
`17.
`
`I have also served on the editorial advisory boards of four
`
`scientific journals including, HIV/AIDS – Research and Palliative Care,
`
`Journal of Biomedical Nanotechnology , Drug Development and Industrial
`
`Pharmacy, and TheScientificWorld Journal – Drug Delivery.
`
`18.
`
`From 1999 to 2006, I served as Assistant and Associate Director of
`
`the Center for Pharmaceutical Science and Technology (“CPST”). The CPST
`
`was the analytical, formulation development, and FDA-registered cGMP
`
`clinical trial manufacturing facility of the College of Pharmacy, University of
`
`Kentucky in Lexington, KY. From 1999 to 2006, working with seven different
`
`clients, I led the CPST’s efforts to complete seven full product development
`
`projects (analytical, formulation, manufacturing, quality control) leading to
`
`the successful submission of Investigational New Drug Applications and the
`
`commencement of human clinical trials. In 2007, the CPST became a for-profit
`
`company under the name of Coldstream Laboratories, Inc.
`
`19.
`
`I have previously served as an expert patent witness in the areas of
`
`DRL - EXHIBIT 1003
`DRL11
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`MonoSol2003-0016
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`
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`oral sustained release drug delivery systems, and topical delivery systems for
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`buccal, nasal, and skin application. In the last 6 years, I have been retained 6
`
`times
`
`and prepared expert reports or declarations and was deposed in each of these
`
`cases. I testified in federal court twice, once at a Markman hearing and once at
`
`trial.
`
`20.
`
`In addition to teaching at the University, and advising and
`
`mentoring in science education, I am active in invited talks and seminars,
`
`particularly on nanotechnology-based drug delivery systems for cancer and
`
`vaccine applications, as well as oral (trans)mucosal delivery and mucosal
`
`immunization by the buccal and nasal routes of administration. In the past
`
`about 20 years, I have been invited to give more than 80 scientific talks at 15
`
`different universities, 7 different national or international meeting venues in
`
`the United States, 12 different pharmaceutical companies, 12 different
`
`countries, and several other venues.
`
`21. My June 2016 CV also shows that I have published a number of
`
`peer- reviewed manuscripts on the creation, development, and testing of
`
`buccal and transbuccal drug, gene, and vaccine delivery systems, and the
`
`characterization of such delivery systems. The manuscripts have pertained to
`
`mucoadhesive thin- films, mucoadhesive film-forming gels, and the use of
`
`near-infra-red to determine the content and content uniformity of
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`DRL - EXHIBIT 1003
`DRL12
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`MonoSol2003-0017
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`
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`drug-containing thin-films. These peer- reviewed manuscripts pertaining to
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`oral (buccal) delivery have been published in Pharmaceutical Research,
`
`Clinical Cancer Research, Journal of Pharmaceutical and Biomedical Analysis,
`
`Journal of Pharmaceutical Sciences, among others.
`
`22. Outside of the academia, I have been advisor and consultant to the
`United States government and leading chemical and pharmaceutical
`
`companies, as well as nascent biotechnology concerns. I have advised the
`
`Federal Trade Commission, GlaxoSmithKline (Parsippany, NJ), Merck & Co.,
`
`Inc. (West Point, PA), and Isis Pharmaceuticals, Inc. (Carlsbad, CA), among
`
`others.
`
`23. Therefore, I believe I am well qualified to serve as a technical
`
`and scientific expert in this matter based on my educational background and
`
`research, industry, and teaching experience.
`
`B.
`
`B.BasesBasis for Opinion and Materials Considered
`
`24.
`
`15.Exhibit 1048 includes a list of the materials I considered, in addition
`
`to my experience, education, and training, in providing the opinions contained
`
`herein.
`
`C.
`
`C.Scope of Work
`
`25.
`
`16.I have been retained by TevaDr. Reddy’s as a technical expert in
`
`this matter to provide various opinions regarding the ’150 patent. I receive
`
`$4001,100 per hour for my services and $500 per hourincluding for deposition
`
`testimony and $300 per hour for travel time. No part of my compensation is
`DRL - EXHIBIT 1003
`DRL13
`
`MonoSol2003-0018
`
`
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`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. However, in 2003 I was retained by Dr. Reddy's Laboratories, Inc. in
`
`Upper Saddle River, New Jersey on a limited basis to serve on a panel of
`
`experts that met one time to advise the company on the future of medicine and
`
`the role of engineering and pharmaceutical sciences. I do not have any current or
`
`past
`
`affiliation with MonoSol RX, LLC, or any of the named inventors on the ’150
`
`patent.
`
`II.Summary of Opinions
`II.
`SUMMARY OF OPINIONS
`
`26.
`
`17.I understand that TevaDr. Reddy’s is challenging the validity of
`
`claims 1, 4-10, and 13- 1-18 of the ’150 patent (“the Challenged Claims”).
`
`27.
`
`18.In reaching these opinions, I have reviewed the ’150 patent as well
`
`as portions of the file history of the ’150 patent. I have also reviewed references and
`
`articles, which I describe in greater detail below, and the materials listed in Exhibit
`
`1048 attached hereto. I have also relied upon my education, background, and
`
`experience in reaching the conclusions and in forming the opinions set forth herein.
`
`19.To summarize, for the reasons set forth below, it is my opinion that the Challenged Claims
`
`of the ’150 patent arewould be obvious to a person of ordinary skill in the art in view of the
`
`prior art, including art that discloses the use of hydrophilic cellulosic polymers and both low
`
`and high molecular weight polyethylene oxide (“PEO”) to form uniform film products
`DRL - EXHIBIT 1003
`DRL14
`
`MonoSol2003-0019
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`
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`containing active pharmaceutical ingredients.
`
`28.
`
`20.For the reasons set forth below, the Challenged Claims are entitled
`
`to a priority date no earlier than April 22, 2008. Alternatively, to the extent the
`
`Board determines that the specification of the ’150 patent contains a sufficient
`
`written description to support the claimed invention, the Challenged Claims are
`
`entitled to a
`
`priority date no earlier than May 23, 2003. It is my further opinion that the
`
`Challenged Claims would have been obvious to a person of ordinary skill in the art
`
`as of May 23, 2003 and April 22, 2008. The Challenged Claims of the ’150 patent
`
`represent no more than a combination of familiar elements assembled according to
`
`known methods to yield predictable results.
`
`29.
`
`21.It is my opinion that one of ordinary skill in the art would have
`
`considered the ‘150 patent obvious in view of the teachings of WO 2000/042992
`
`to Chen in combination with US 4,713,243 to Schiraldi. Chen teaches
`
`hydrocolloid films for mucosal drug delivery, including films containing an
`
`opioid. The hydrocolloid can contain a hydrophilic cellulosic polymer, such as
`
`HPMC or HPC and can contain polyethylene oxide. Chen discloses Example
`
`11, a mucoadhesive film containing 77.8% Polyox®WSR N-10, a polyethylene
`
`oxide having an average molecular weight of 100,000 Daltons (or Da), which
`
`meets the requirement of claim 1 of the ‘150 patent for “about 60% or more”
`
`of the low molecular weight PEO. Schiraldi teaches the use of a high molecular
`
`DRL - EXHIBIT 1003
`DRL15
`
`MonoSol2003-0020
`
`
`
`weight polyethylene oxide for mucoadhesive films.
`
`For example Schiraldi
`
`teaches a bioadhesive layer of a mucosal film having 60% w/w polyethylene
`
`oxide homopolymer (Polyox WSR N-301, molecular weight of 4,000,000 Da).
`
`Both Chen and Schiraldi teach varying the ratios of film polymers to control
`
`film properties. Importantly, Chen states “…the film may be formed using a
`
`mixture of
`
`two or more types of the same hydrocolloid that differ only in molecular weight
`
`and/ or degree of substitution.” Chen also states “The dosage unit may release
`
`the active agent over a period of time that is determined by a number of
`
`different factors.” Schiraldi teaches that “by varying the ratios of the above
`
`polymers both the solubility and adhesive properties of each layer of film may
`
`be controlled.” Thus, it is my opinion that one of ordinary skill reading Chen
`
`and Schiraldi would be highly motivated to vary the amounts of the low and
`
`high molecular weight polyethylene oxide to achieve the desired effects
`
`including, but not limited to drug solubility, mucoadhesion and drug release
`
`rate.
`
`30.
`
`It is also my opinion that one of ordinary skill in the art would have
`
`recognized that a mucosally-adhesive, water-soluble film product as claimed in the
`
`Challenged Claims of the ’150 patent was already disclosed in Yang. Yang
`
`disclosed various film compositions containing combinations of low molecular
`
`weight polyethylene oxide (PEO), higher molecular weight PEO and hydrophilic
`
`DRL - EXHIBIT 1003
`DRL16
`
`MonoSol2003-0021
`
`
`
`cellulosic polymers. A person of ordinary skill in the art would understand from
`
`Yang’s disclosures that the exact proportions of such film compositions could be
`
`readily and easily modified using the teachings of the prior art to obtain a film
`
`composition with the qualities described and claimed in the ’150 patent. One of
`
`ordinary skill in the art would also have recognized that combining small amounts
`
`of high molecular weight PEOs with low molecular weight PEOs improved the tear
`
`resistance of the final film. From Yang, one of ordinary skill in the art would have
`
`further recognized that films having 60% or greater amounts of low molecular
`
`weight PEO in such combinations resulted in faster dissolution of the films when in
`
`contact with mucousmucosal membranes.
`
`22.Even before the publication of Yang, the properties of the claimed film compositions
`
`were well-described in the art and were well-known to a person of ordinary skill. The use of
`
`PEO in film compositions for use in delivering active pharmaceutical agents was disclosed
`
`in at least Schiraldi, including, in the use of analgesics. This reference Schiraldi also teaches
`
`the use of cellulosic polymers in combination with PEO to produce a film with desirable
`
`structural characteristics. The combination of low molecular weight PEO and high molecular
`
`weight PEO in such compositions was a well-known means of further manipulating the
`
`structural properties of film compositions to attain desired thickness, uniformity, and tensile
`
`and shear strength. Such film compositions were routinely employed by those of ordinary
`
`skill in the art. As such, it would have been obvious to those of ordinary skill in the art to
`
`combine low molecular weight PEO, higher molecular weight PEO, and a hydrophilic
`
`DRL - EXHIBIT 1003
`DRL17
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`MonoSol2003-0022
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`
`
`cellulosic polymer, and modify the proportions of each component of the film composition
`
`to attain a film with the claimed structural properties and uniformity.
`
`III.Legal Standards
`III.
`LEGAL STANDARDS
`
`31.
`
`23.I understand that a preponderance of evidence must be
`
`presented to render a patent claim invalid in this proceeding.
`
`32.
`
`24.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
`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) (2006).
`
`25.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 skill 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 in doing so may be found in the teachings of the
`
`DRL - EXHIBIT 1003
`DRL18
`
`MonoSol2003-0023
`
`
`
`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 elements according to
`
`known methods is likely to be obvious when it does no more than yield predictable
`
`results.
`
`33.
`
`26.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.
`
`34.
`
`27.I understand that a claim may be obvious when it is the result of
`
`combining familiar elements according to known methods to achieve predictable
`
`results. The claim is obvious when a person of ordinary skill in the art would have
`
`been motivated to combine the teachings of the prior art and would have had a
`
`reasonable expectation of success in doing so.
`
`35.
`
`28.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.
`
`DRL - EXHIBIT 1003
`DRL19
`
`MonoSol2003-0024
`
`
`
`36.
`
`29.I have relied upon this understanding of the applicable legal
`
`standards in reaching my opinions set forth in this declaration.
`
`IV.Person of Ordinary Skill in the Art
`IV.
`PERSON OF ORDINARY SKILL IN THE ART
`
`37.
`
`30.It is my opinion that in the context of the ’150 patent, a person of
`
`ordinary skill in the art would include a person who possesses a Master’s degree or
`
`Ph.D. degree in pharmaceutical sciences, chemistry, or a related filed, and a
`
`number ofat least 5 years of experience with a Master’s degree or at least 2
`
`years of experience with a Ph.D. degree.
`
`V.
`
`V.TheTHE ’150 PatentPATENT
`
`38.
`
`31.I have read the ’150 patent, entitled “Polyethylene Oxide-based
`
`Films and Drug Delivery Systems Made Therefrom.” The ’150 patent was filed on
`
`April 22, 2008, as U.S. Patent Application No. 12/107,389, and is a
`
`divisiondivisional application of U.S. Patent Application No. 10/856,176, which
`
`was filed on May 28, 2004 and is now U.S. Patent No. 7,666,337, which is a
`
`continuation-in-part of application No. PCT/US02/032575, filed on Oct. 11, 2002,
`
`and a continuation-in-part of application No. PCT/US02/32594, filed on Oct. 11,
`
`2002, and a continuation-in- part of application No. PCT/US02/32542, filed on Oct.
`
`11, 2002
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