`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________________
`
`MYLAN PHARMACEUTICALS INC.,
`
`
`Petitioner,
`
`v.
`
`COSMO TECHNOLOGIES LIMITED,
`Patent Owner.
`
`U.S. Patent No. 9,320,716 to Villa et al.
`Case No..: IPR2017-01035
`
`U.S. Patent No. 8,784,888 to Villa et al.
`Case No.: IPR2017-01034
`____________________
`
`
`DECLARATION OF ANTHONY PALMIERI III, PH.D, R.PH.
`
`
`
`
`
`
`
`
`
`
`
`MYLAN Ex 1006, Page 1
`
`

`

`Declaration of Anthony Palmieri III, Ph.D, R.Ph.
`
`
`Table of Contents
`
`I.
`
`INTRODUCTION ....................................................................................... 1
`
`II. MY EXPERIENCE AND QUALIFICATIONS ........................................... 2
`
`III. LIST OF MATERIALS CONSIDERED...................................................... 6
`
`IV. LEGAL STANDARD .................................................................................. 9
`A. Anticipation ......................................................................................10
`B.
`Obviousness ......................................................................................11
`
`V.
`
`PERSON OF ORDINARY SKILL IN THE ART (“POSA”) ......................13
`
`VI. THE VILLA PATENTS .............................................................................14
`
`VII. CLAIM CONSTRUCTION ........................................................................17
`
`VIII. SCOPE AND CONTENT OF THE PRIOR ART .......................................19
`A.
`Controlled Release Oral Compositions .............................................20
`B.
`Budesonide .......................................................................................24
`
`IX.
`
`B.
`
`INVALIDITY OF THE ’716 PATENT ......................................................24
`A.
`The ’584 Patent Anticipates Claims 1-29 of the ’716 Patent .............24
`1.
`Independent Claims ................................................................24
`a)
`“at least one lipophilic compound” ...............................30
`b)
`“at least one hydrophilic compound” ............................31
`c)
`“at least one amphiphilic compound” ............................31
`d)
`“macroscopically homogenous structure controls
`the release of the budesonide” .......................................32
`Dependent Claims ...................................................................34
`2.
`The ’584 Patent Renders Obvious Claims 1-29 of the ’716 Patent
`..........................................................................................................38
`1.
`Claim 1 ...................................................................................39
`a)
`“A
`controlled
`release oral pharmaceutical
`composition comprising: (i) budesonide in an
`amount effective to treat intestinal inflammatory
`disease” .........................................................................39
`“a macroscopically
`homogenous
`structure
`comprising” ..................................................................40
`“at least one lipophilic compound” ...............................42
`
`b)
`
`c)
`
`i
`
`MYLAN Ex 1006, Page 2
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`

`

`d)
`e)
`
`f)
`
`g)
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`Declaration of Anthony Palmieri III, Ph.D, R.Ph.
`
`“at least one hydrophilic compound” ............................44
`“wherein
`the macroscopically
`homogenous
`structure controls the release of the budesonide” ...........45
`“a gastro-resistant coating on the macroscopically
`homogenous structure that prevents release of
`budesonide in the stomach” ..........................................45
`“wherein
`the macroscopically
`homogenous
`structure is a tablet” ......................................................46
`Claims 6, 12, and 22: “at least one amphiphilic compound”
`................................................................................................46
`Claims 2 and 13: “wherein the gastro-resistant coating is .
`. . methacrylic acid polymers and cellulose derivatives” ........48
`Claims 3-5 and 14-16: “wherein the at least one
`hydrophilic compound is . . . a hydroxyalkyl cellulose” ..........49
`Claims 7, 8, 17 and 18: “wherein the at least one
`amphiphilic compound . . . lecithin” .......................................50
`Claims 9, 10, 19 and 20: “wherein the at least one
`lipophilic compound is selected from the group consisting
`of an unsaturated or hydrogenated alcohol or fatty acid,
`salt, ester, or amide thereof . . .”/“lipophilic compound is
`stearic acid” ............................................................................50
`Claims 11, 21 and 23: “The controlled release oral
`pharmaceutical composition . . . further comprising . . . an
`acrylic acid polymer” ..............................................................52
`Claims 24, 25 and 26: “wherein the macroscopically
`homogenous
`structure
`comprises microcrystalline
`cellulose” ................................................................................53
`Claims 27, 28 and 29: “A method for treating intestinal
`inflammatory disease comprising administering to a
`patient
`the controlled
`release oral pharmaceutical
`composition according to claim [1/12/22]” .............................53
`10. Reasonable Expectation of Success .........................................54
`The ’388 Patent Anticipates Claims 1-7, 9, 11-17, 19, and 21-29
`of the ’716 Patent ..............................................................................54
`1.
`Independent Claims ................................................................54
`2.
`Dependent Claims ...................................................................63
`The ’388 Patent Renders Obvious Claims 1-29 of the ’716 Patent
`..........................................................................................................66
`1.
`Claim 1 ...................................................................................66
`
`7.
`
`8.
`
`9.
`
`C.
`
`D.
`
`ii
`
`MYLAN Ex 1006, Page 3
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`

`

`Declaration of Anthony Palmieri III, Ph.D, R.Ph.
`
`
`a)
`
`b)
`
`f)
`
`g)
`
`c)
`d)
`e)
`
`release oral pharmaceutical
`controlled
`“A
`composition comprising: (i) budesonide in an
`amount effective to treat intestinal inflammatory
`disease” .........................................................................66
`“a macroscopically
`homogenous
`structure
`comprising” ..................................................................68
`“at least one lipophilic compound” ...............................68
`“at least one hydrophilic compound” ............................69
`“wherein
`the macroscopically
`homogenous
`structure controls the release of the budesonide” ...........69
`“a gastro-resistant coating on the macroscopically
`homogenous structure that prevents release of
`budesonide in the stomach” ..........................................69
`“wherein
`the macroscopically
`homogenous
`structure is a tablet” ......................................................70
`Claims 6, 12, and 22: “at least one amphiphilic compound”
`................................................................................................70
`Claims 2 and 13: “wherein the gastro-resistant coating is .
`. . methacrylic acid polymers and cellulose derivatives” ........71
`Claims 3-5 and 14-16: “wherein the at least one
`hydrophilic compound is . . . a hydroxyalkyl cellulose” ..........72
`Claims 7, 8, 17 and 18: “wherein the at least one
`amphiphilic
`compound
`is
`.
`.
`.
`.[phosphatidylcholines/lecithin]” ............................................72
`Claims 9, 10, 19 and 20: “wherein the at least one
`lipophilic compound is selected from the group consisting
`of an unsaturated or hydrogenated alcohol or fatty acid,
`salt, ester, or amide thereof . . .”/“lipophilic compound is
`stearic acid” ............................................................................74
`Claims 11, 21 and 23: “The controlled release oral
`pharmaceutical composition . . . further comprising . . . an
`acrylic acid polymer” ..............................................................75
`Claims 24, 25 and 26: “wherein the macroscopically
`homogenous
`structure
`comprises microcrystalline
`cellulose” ................................................................................76
`Claims 27, 28 and 29: “A method for treating intestinal
`inflammatory disease comprising administering to a
`patient
`the controlled
`release oral pharmaceutical
`composition according to claim [1/12/22]” .............................76
`10. Reasonable Expectation of Success .........................................77
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`7.
`
`8.
`
`9.
`
`iii
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`MYLAN Ex 1006, Page 4
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`

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`Declaration of Anthony Palmieri III, Ph.D, R.Ph.
`
`
`E.
`
`The ‘388 Patent in View of the ’584 Patent Renders Obvious
`Claims 8, 10, 18, and 20 of the ’716 Patent .......................................77
`1.
`Claims 8 and 18: wherein the at least one amphiphilic
`compound is . . . . lecithin” .....................................................77
`Claims 10 and 20: “wherein the at least one lipophilic
`compound is stearic acid” .......................................................79
`
`2.
`
`X.
`
`b)
`c)
`
`d)
`
`e)
`
`f)
`
`
`
`
`
`
`
`INVALIDITY OF THE ’888 PATENT ......................................................80
`A.
`The ’120 Patent and ’584 Patent Renders Obvious Claims 1-9 of
`the ’888 Patent ..................................................................................80
`1.
`Claim 1 ...................................................................................81
`a)
`“A
`controlled
`release oral pharmaceutical
`composition consisting essentially of” ..........................81
`“a tablet core consisting essentially of” .........................81
`“budesonide
`in an amount effective
`to
`treat
`intestinal inflammatory disease” ...................................81
`“a macroscopically homogeneous composition
`comprising” ..................................................................82
`“at least one lipophilic excipient” .......................84
`“at least one amphiphilic excipient” ....................84
`“at least one hydrogel-forming hydrophilic
`excipient other than a gum” ................................85
`“wherein said budesonide is dispersed in said
`macroscopically homogeneous composition”................86
`“a coating on said tablet core, said coating
`consisting essentially of a gastro-resistant film” ............87
`Reasonable Expectation of Success ...............................87
`g)
`Claims 2, 4, 6, 8: “at least one hydrogel-forming
`hydrophilic excipient comprises at least one hydroxyalkyl
`cellulose” ................................................................................88
`Claim 3: “said gastro-resistant film consists essentially of
`at least one methacrylic acid polymer” ....................................88
`Claims 5 and 9: “at least one lipophilic excipient
`comprises stearic acid or magnesium stearate”........................89
`Claim 7: “at least one amphiphilic excipient comprises
`lecithin” ..................................................................................89
`The ’584 Patent Renders Obvious Claims 1-9 of the ’888 Patent ......90
`1.
`Claim 1 ...................................................................................90
`a)
`“A
`controlled
`release oral pharmaceutical
`composition” .................................................................90
`
`2.
`
`3.
`
`4.
`
`5.
`
`B.
`
`iv
`
`MYLAN Ex 1006, Page 5
`
`

`

`b)
`c)
`
`d)
`
`e)
`
`f)
`
`
`
`
`
`
`
`Declaration of Anthony Palmieri III, Ph.D, R.Ph.
`
`“a tablet core consisting essentially of” .........................90
`“budesonide
`in an amount effective
`to
`treat
`intestinal inflammatory disease” ...................................91
`“a macroscopically homogeneous composition” ...........91
`“at least one lipophilic excipient” .......................92
`“at least one amphiphilic excipient” ....................92
`“at least one hydrogel-forming hydrophilic
`excipient other than a gum” ................................93
`“wherein said budesonide is dispersed in said
`macroscopically homogeneous composition”................94
`“a coating on said tablet core, said coating
`consisting essentially of a gastro-resistant film” ............94
`’584 patent’s Semi-Permeable Layer ............................95
`g)
`Claims 2, 4, 6, 8: “at least one hydrogel-forming
`hydrophilic excipient comprises at least one hydroxyalkyl
`cellulose” ................................................................................99
`Claim 3: “said gastro-resistant film consists essentially of
`at least one methacrylic acid polymer” .................................. 100
`Claims 5 and 9: “at least one lipophilic excipient
`comprises stearic acid or magnesium stearate”...................... 101
`Claim 7: “at least one amphiphilic excipient comprises
`lecithin” ................................................................................ 101
`Reasonable Expectation of Success ....................................... 102
`6.
`The ’208 Publication Anticipates Claims 1-9 of the ’888 Patent ..... 102
`a)
`“Other Than Gum” Limitation .................................... 102
`b)
`The Priority Specifications are Ambivalent as to the
`Hydrophilic Excipient ................................................. 103
`Disclosure of the ’208 Publication ........................................ 108
`
`2.
`
`3.
`
`4.
`
`5.
`
`2.
`
`C.
`
`XI. SECONDARY CONSIDERATIONS ....................................................... 113
`
`v
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`MYLAN Ex 1006, Page 6
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`
`
`I, Anthony Palmieri III, Ph.D., R.Ph. do hereby declare and state as follows:
`
`1.
`
`I have been asked to provide testimony as to what one of ordinary skill
`
`in the art would have understood with respect to the patents at issue and various prior
`
`art discussed herein. I provide this testimony below:
`
`I.
`
`INTRODUCTION
`
`2.
`
`I am over the age of eighteen (18) and otherwise competent to make
`
`this Declaration.
`
`3.
`
`I have been retained on behalf of Petitioner for the above-captioned
`
`inter partes reviews (“IPRs”). I am being compensated for my time in connection
`
`with this IPR at my standard consulting rate, which is $500 per hour for all work
`
`conducted in Gainesville, FL and $4000 per day for all work conducted outside of
`
`Gainesville, FL. My compensation does not depend in any way on the outcome of
`
`any of the IPRs.
`
`4.
`
`It is my understanding that the Petitions for Inter Partes Review in this
`
`matter involves U.S. Patent No. 9,320,716 (“the ’716 patent”) (EX1001) and U.S.
`
`Patent No. 8,784,888 (“the ’888 patent”) (EX1002) (collectively, “the Villa
`
`Patents”).
`
`5.
`
`Both Villa Patents name Roberto Villa, Massimo Pedrani, Mauro Ajani,
`
`and Lorenzo Fossati as the purported inventors. I understand that the ’716 patent is
`
`a continuation of the ’888 patent.
`
`1
`
`MYLAN Ex 1006, Page 7
`
`

`

`
`
`6.
`
`It is also my understanding that the priority date of the Villa Patents is
`
`June 9, 2000, the filing date of the International Patent Application No.
`
`PCT/EP00/05356. I further understand that the Villa Patents are assigned to Cosmo
`
`Technologies Limited (“Cosmo,” “Patentee,” or “Patent Owner”).
`
`7.
`
`As explained below, my opinion is that all claims of the Villa Patents
`
`would have been invalid for anticipation and/or obviousness. Budesonide oral
`
`compositions were known and all the purported inventors did was use known
`
`excipients in known ways to create a budesonide oral tablet composition. See, e.g.,
`
`infra ¶¶ 49-56.
`
`II. MY EXPERIENCE AND QUALIFICATIONS
`
`8.
`
`I am an expert in the field of pharmaceutical formulation, and I have
`
`been an expert in this field since at least 1985. In forming my opinions, I have relied
`
`on my knowledge, training, and experience in the pertinent art.
`
`9.
`
`I received my B.S. and M.S. in Pharmacy from the University of Rhode
`
`Island in Kingston, Rhode Island. I received my Ph.D. in Pharmaceutics from the
`
`University of Georgia in Athens, Georgia. The title of my Dissertation was
`
`“Microencapsulation of drugs suspended in an oil: preparation and dissolution
`
`properties of microcapsules of prednisone and hydrocortisone.” Throughout my
`
`career, my research interests have included drug form design, dissolution,
`
`2
`
`MYLAN Ex 1006, Page 8
`
`

`

`
`
`microencapsulation and other sustained (i.e., controlled) release delivery systems
`
`and drug release from suppositories.
`
`10. From 1975 to 1980, I was Assistant Professor of Pharmaceutics, and
`
`from 1980 to 1984, I was a tenured Associate Professor of Pharmaceutics at the
`
`University of Wyoming in Laramie, Wyoming. During my time at the University of
`
`Wyoming I taught courses in dose form design, including sustained release of pain
`
`relievers, physical pharmacy, problems in pharmacy and dissolution, among others.
`
`11. From 1984 to 1988, I was Senior Patent Liaison Scientist in the
`
`Research and Development Division of the Upjohn Company in Kalamazoo,
`
`Michigan. From 1988 to 1992, I was a Manager of Intellectual Property at Upjohn.
`
`From 1992 to 1994, I was a Manager of Intellectual Property and Research Contracts
`
`at Upjohn. From 1994 to 1996, I was a Manager of Technology Protection and
`
`Tracking at Upjohn. In these positions my responsibilities included patent decisions,
`
`manuscript review, and negotiation of scientific and monetary terms for research and
`
`scientific collaborations among Upjohn and other companies, academia, and
`
`government agencies.
`
`12. From 1996 to 2000, I was Manager of Technology Protection at
`
`Pharmacia & Upjohn. In this position I had daily interactions with dose form
`
`scientists assisting in evaluation of various dosage forms. Among other patent
`
`duties, I also evaluated commercial potential of inventions, educated the scientific
`
`3
`
`MYLAN Ex 1006, Page 9
`
`

`

`
`
`community on intellectual property issues and assisted in determining patentability
`
`of inventions from a scientific standpoint. While at The Upjohn Company, I had
`
`daily interactions with R&D scientists concerning dose form design and evaluation
`
`of these formulations, including extended release formulations.
`
`13. From 2000 to 2015, I was employed by University of Florida in
`
`Gainesville, Florida. During this time, I held various positions as described below.
`
`14.
`
`I joined the University of Florida in 2000 as an Adjunct Professor of
`
`Pharmaceutics and Assistant Director of the Office of Technology Licensing. In this
`
`position I interacted with faculty in the College of Pharmacy, College of Medicine,
`
`Engineering, and the chemistry department and others on a daily basis to discuss
`
`experiments, experimental design and evaluation of results. I also evaluated the
`
`University’s intellectual property portfolio in the life sciences and provided
`
`assistance in the protection and commercialization of this intellectual property. I
`
`held this position until 2006.
`
`15. From 2006 to 2011, I was a Clinical Assistant Professor of
`
`Pharmaceutics, and from 2011 to 2013, I was Assistant Scholar of Pharmaceutics at
`
`the University of Florida. In 2014, I was promoted to Associate Scholar. In these
`
`position my responsibilities included instructing graduate and undergraduate
`
`students in clinical biochemistry, dose form design, sustained release, and
`
`dissolution. While at the University of Florida I was also the Graduate Student
`
`4
`
`MYLAN Ex 1006, Page 10
`
`

`

`
`
`Coordinator for Pharmaceutics and a member of the Graduate Studies Committee. I
`
`was also a member of numerous research committees for graduate students. I remain
`
`on 5 such research committees helping to direct the Ph.D. student research for their
`
`dissertation. Currently, I am retired.
`
`16.
`
`I am the author of over 80 publications and presentations on
`
`pharmaceutics,
`
`intellectual property, dosage forms, dissolutions, pharmacy
`
`education and the history of pharmacy. By 2001, I was the author of more than 16
`
`peer-reviewed publications on pharmaceutical dosage forms. I am the author of 6
`
`book chapters on pharmaceutical formulations and the author of numerous
`
`monographs for the Handbook of Pharmaceutical Excipients. I have given more
`
`than 40 presentations on pharmacy, intellectual property and related topics. Many
`
`of my research presentations and publications concerned the area of drug release
`
`from dose forms, including sustained release and dissolution. I have also written
`
`chapters on dissolution and was the editor of a well-recognized textbook on
`
`dissolution theory, methodology and practice.
`
`17.
`
`I am on the Editorial Advisory Board of the Journal of Chemical and
`
`Pharmaceutical Sciences and the Research Journal of Pharmaceutical Biological and
`
`Chemical Sciences. I was the Steering Committee chairman for the American
`
`Pharmacists Association’s Handbook of Pharmaceutical Excipients, 2nd edition. I
`
`was the laboratory chair for the 3rd edition and have reviewed as well as written
`
`5
`
`MYLAN Ex 1006, Page 11
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`

`

`
`
`monographs for each edition of the Handbook of Pharmaceutical Excipients which
`
`is the preeminent reference on excipients and the use of excipients in pharmaceutical
`
`dosage form. I am a Fellow of the Academy of Pharmaceutical Research and
`
`Sciences and the past president of that organization.
`
`18. A copy of my curriculum vitae, which includes a complete description
`
`of my education and experience, is attached hereto as EX1007.
`
`III. LIST OF MATERIALS CONSIDERED
`
`19.
`
`In formulating my opinions, I have considered the materials referenced
`
`in this Declaration and those referenced in the Petitions for Inter Partes Review of
`
`the Villa Patents. I also have reviewed the Villa Patents and their respective
`
`prosecution histories as well as each of the documents cited herein in light of the
`
`general knowledge in the state of the art as of June 9, 2000.
`
`Petitioner
`Exhibit #
`1001
`
`1002
`
`1003
`1004
`1005
`1006
`1007
`1008
`
`1009
`
`Description
`
`U.S. Patent No. 9,320,716 to Villa et al., “Controlled Release and
`Taste Masking Oral Pharmaceutical Compositions”
`U.S. Patent No. 8,784,888 to Villa et al., “Controlled Release and
`Taste Masking Oral Pharmaceutical Composition”
`Reserved
`Reserved
`Reserved
`Declaration of Anthony Palmieri III, Ph.D., R.Ph.
`Curricula Vitae of Anthony Palmieri, Ph.D., R.Ph.
`U.S. Patent No. 5,681,584 to Savastano et al., “Controlled Release
`Drug Delivery Device”
`U.S. Patent No. 5,811,388 to Friend et al., “Delivery of Drugs to the
`Lower GI Tract”
`
`6
`
`MYLAN Ex 1006, Page 12
`
`

`

`
`
`1010
`
`1011
`
`U.S. Patent No. 6,239,120 to Hallgren et al., “Method and Means for
`Treating Glomerulonephritis”
`U.S. Patent Appl. Pub. No. 2006/0134208 to Villa et al., “Controlled
`Release and Taste Masking Oral Pharmaceutical Composition”
`1012 Markman Opinion and Order in Cosmo Technologies Limited v.
`Alvogen Pine Brook, LLC., C.A. No. 15-193-LPS, ECF Nos. 167, 168
`(D. Del. Sept. 7, 2016).
`Amendment and Response to Advisory Action filed on February 21,
`2014 in U.S. Patent Appl. No. 13/617,138
`Substitute Specification (Clean Copy) filed on April 29, 2013 in U.S.
`Patent Appl. No. 13/617,138
`Amendment After Final filed on April 29, 2013 in U.S. Patent Appl.
`No. 13/617,138
`Amendment and Response to Office Action filed on July 1, 2013 in
`U.S. Patent Appl. No. 13/617,138
`U.S. Patent No. 6,607,751 to Odidi et al., “Controlled Release
`Delivery Device for Pharmaceutical Agents Incorporating Microbial
`Polysaccharide Gum”
`Campieri et al., Oral Budesonide is as Effective as Oral Prednisolone
`in Active Crohn’s Disease, Gut, 41:209-214 (1997)
`Reserved
`Reserved
`Reserved
`PCT International Publication No. WO 96/36318, “Three-Phase
`Pharmaceutical Form With Constant and Controlled Release of
`Amorphous Active Ingredient for Single Daily Application”
`U.S. Patent No. 5,342,625
`to Hauer et al., “Pharmaceutical
`Compositions Comprising Cyclosporins”
`PCT International Publication No. WO 99/39700, “Pharmaceutical
`compositions in form of nanoparticles comprising lipidic substances
`and amphiphilic substances and related preparation process”
`FDA Inactive Ingredient Guide 1996/1997
`Handbook of Pharmaceutical Excipients (Wade and Weller, eds., 2d
`ed. 1994)
`Reserved
`Remington: The Science and Practice of Pharmacy, Vol. 1 (1995)
`Reserved
`Hawley’s Condensed Chemical Dictionary (John Wiley & Sons, Inc.,
`13th ed. 1997)
`
`1019
`1020
`1021
`1022
`
`1013
`
`1014
`
`1015
`
`1016
`
`1017
`
`1018
`
`1023
`
`1024
`
`1025
`1026
`
`1027
`1028
`1029
`1030
`
`7
`
`MYLAN Ex 1006, Page 13
`
`

`

`
`
`1031
`1032
`1033
`
`1034
`
`1035
`
`1036
`
`1037
`
`1038
`
`1039
`
`1040
`
`1041
`
`1042
`1043
`
`1044
`
`to Alan Rhodes, “Slow Release
`
`Reserved
`Entocort® EC Highlights of Prescribing Information
`Svensson et al., Hydration of an Amphiphilic Excipient, Gelucire
`44/14, 2004, <hal-00015990>
`U.S. Patent No. 6,395,300 to Straub et al., “Porous Drug Matrices and
`Methods of Manufacture Thereof”
`Flanders et al., The Control of Drug Release From Conventional Melt
`Granulation Matrices, Drug Development & Industrial Pharmacy,
`13(6):1001-1022 (1987)
`Gandhi et al., Extrusion and Spheronization in the Development of
`Oral Controlled-Release Dosage Forms, Pharmaceutical Sci. & Tech.
`Today 2(4):160 (1999)
`US Patent No. 4,880,830
`Formulation”
`Daly et al., The Effect of Anionic Surfactants on the Release of
`Chlorpheniramine from a Polymer Matrix Tablet, Int’l J. of
`Pharmaceutics, 18:201-05 (1984)
`S.S. Davis, The Design and Evaluation of Controlled Release Dosage
`Forms for Oral Delivery, S.T.P. Pharma 3(5):412-417 (1987)
`U.S. Patent No. 5,849,327 to Berliner et al., “Delivery of Drugs to the
`Lower Gastrointestinal Tract”
`U.S. Patent No. 5,643,602 to , “Oral Composition for the Treatment
`of Inflammatory Bowel Disease”
`U.S. Provisional Application No. 60/080,274 filed on April 1, 1998
`Gliko-Kabir et al., Low Swelling, Crosslinked Guar and Its Potential
`Use as a Colon-Specific Drug Carrier, Pharm. Research 15(7):1019-
`1025 (1998)
`See A Blume, B Arnold, HU Weltzien, Effects of a synthetic
`lysolecithin analog on
`the phase
`transition of mixtures of
`phosphatidylethanolamine and phosphatidylcholine, FEBS Letters
`(1976)
`Qiu et al., Design of sustained-release matrix systems for a highly
`water-soluble compound, ABT-089, Int’l J. of Pharmaceutics 157:43-
`52 (1997)
`1046 M. Efentakis et al., The Influence of Surfactants on Drug Release from
`a Hydrophobic Matrix, Int’l J. Pharm. 70:153-58 (1991)
`Uceris® website, https://www.uceris.com/tablet/ (accessed on March
`5, 2017)
`
`1045
`
`1047
`
`8
`
`MYLAN Ex 1006, Page 14
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`

`

`
`
`
`
`1048
`
`1049
`1050
`
`1051
`
`1052
`
`1053
`1054
`1055
`1056
`1057
`
`1058
`
`1059
`
`1060
`1061
`
`1062
`
`Santarus’ CEO Discusses FDA Approval Of UCERIS (Budesonide)
`For
`The Induction Of Remission In Patients With Active, Mild To
`Moderate
`Ulcerative Colitis (Transcript) (Jan. 15, 2013)
`Uceris® Instant Savings Program
`Transcript of the Second Quarter 2014 Earnings Conference Call of
`Salix Pharmaceuticals, Ltd.
`L.W. Doner, Determining Sugar Composition of Food Gum
`Polysaccharides by HPTLC, Chromatographia 2001, 53, May (No.
`9/10)
`Amendment filed on January 15, 2013 in U.S. Patent Appl. No.
`13/617,138
`Specification of U.S. Patent Application No. 10/009,532
`Specification of 12/210,969 application
`Specification of 13/249,839 application
`Specification of 13/462,409 application
`Final Office Action of March 6, 2013 in U.S. Patent Appl. No.
`13/617,138
`Applicant-Initiated Interview Summary of April 23, 2013 in U.S.
`Patent Appl. No. 13/617,138
`Original Specification as field on September 14, 2012 in U.S. Patent
`Appl. No. 13/617,138
`Orange Book Listing of Uceris® (accessed on March 8, 2017)
`Hawley’s Condensed Chemical Dictionary (John Wiley & Sons, Inc.,
`13th ed. 1997)
`N. Robinson, Surface Interaction of Lecithin and Lysolecithin, J. of
`Pharmacy and Pharmacology, 12(1) 609-616 (1960)
`
`IV. LEGAL STANDARD
`
`20. Although I am not a lawyer, I provide my general understanding of the
`
`anticipation and obviousness analysis, and I used these principles in conducting my
`
`analysis and drawing any conclusions.
`
`9
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`MYLAN Ex 1006, Page 15
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`

`
`
`21.
`
`I understand that the first step in determining whether a patent claim
`
`would have been anticipated or obvious is to construe the claims to determine claim
`
`scope and meaning. I understand that in Inter Partes Review proceedings the claim
`
`terms are generally given the broadest reasonable interpretation, i.e., their ordinary
`
`and customary meaning as would have been understood by a POSA at the time, in
`
`the context of the entire patent disclosure.
`
`A. Anticipation
`
`22.
`
`I understand that anticipation requires that each and every element of
`
`the claimed invention be disclosed expressly or inherently in a single prior art
`
`reference.
`
`23.
`
`I also understand that an element may be inherent in the prior art where
`
`the prior art necessarily functions in accordance with or includes the claimed
`
`limitations. I am also informed that inherency may exist even if a POSA would not
`
`appreciate or recognize the inherent characteristics of the prior art, as the discovery
`
`of a previously-unappreciated property does not make an old composition
`
`patentable.
`
`24.
`
`I also understand that a prior art reference must enable a POSA to make
`
`and use a claimed invention in order to anticipate a patent claim.
`
`25.
`
`I understand that it is appropriate to consider additional references in
`
`the context of analyzing anticipation where a reference is silent about an inherent
`
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`MYLAN Ex 1006, Page 16
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`

`
`
`characteristic and to determine whether the reference gives possession of the
`
`invention to a POSA.
`
`B. Obviousness
`
`26.
`
`I understand that a patent claim is invalid if the differences between the
`
`claimed invention and prior art are such that the subject matter as a whole would
`
`have been obvious at the time the invention was made to a POSA.
`
`27.
`
`I have been told the following factors are used in making an
`
`obviousness determination: a) the scope and content of the prior art; b) the
`
`differences between the prior art and the claimed invention; c) the level of ordinary
`
`skill in the pertinent art; and d) any secondary considerations evidencing
`
`nonobviousness.
`
`28.
`
`I also understand that obviousness can be established by combining or
`
`modifying the teachings of the prior art. A claimed invention can be obvious when,
`
`for example, there is some teaching, suggestion, or motivation in the prior art that
`
`would have led a POSA to modify the prior art reference or to combine prior art
`
`reference teachings to arrive at the claimed invention.
`
`29.
`
`I also understand that the prior art references themselves do not have to
`
`provide an explicit teaching, suggestion, or motivation to combine prior art
`
`teachings; rather, the analysis may rely on interrelated teachings, market demands,
`
`the background knowledge possessed by a POSA, and/or common sense. Put
`
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`MYLAN Ex 1006, Page 17
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`

`

`
`
`another way, the motivation to combine or modify prior art references can come
`
`from any reason to do so, and is not limited to the reasons that may have motivated
`
`the patentee.
`
`30.
`
`I am also informed that a combination of familiar elements according
`
`to known methods is likely to be obvious when it does no more than yield predictable
`
`results. I also understand that when a person of ordinary skill would have reached
`
`the claimed invention through routine experimentation, the invention may be
`
`deemed obvious.
`
`31.
`
`I understand that various rationales are utilized to determine whether a
`
`claim
`
`is obvious,
`
`including, among others:
`
`(i) simple substitution or
`
`interchangeability of one known element for another to obtain predictable results;
`
`(ii) use of known techniques to improve similar methods or products in the same
`
`way; (iii) applying a known technique to a known method or product ready for
`
`improvement to yield predictable results; (iv) “obvious to try”—choosing from a
`
`finite number of identified, predictable solutions, with a reasonable expectation of
`
`success; and (v) known work in one field of endeavor may prompt variations of it
`
`for use in either the same field or a different one based on design incentives or other
`
`market forces if the variations would have been predictable to one of ordinary skill
`
`in the art.
`
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`MYLAN Ex 1006, Page 18
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`
`
`32. As stated above, I understand that secondary considerations of non-
`
`obviousness are part of the obviousness inquiry. I understand that these secondary
`
`co