IPR2020-00084
`Patent 9,089,519
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`_________________
`
`PROLLENIUM US INC.,
`Petitioner,
`
`v.
`
`ALLERGAN INDUSTRIE, SAS,
`Patent Owner.
`
`_________________
`
`Case IPR2020-00084
`U.S. Patent 9,089,519
`_________________
`
`PATENT OWNER RESPONSE
`
`
`
`
`
`

`

`IPR2020-00084
`Patent 9,089,519
`
`I.
`II.
`
`2.
`3.
`
`4.
`5.
`6.
`7.
`
`TABLE OF CONTENTS
`INTRODUCTION .......................................................................................... 1
`BACKGROUND ............................................................................................ 4
`A.
`The POSA Faced Intricacies And Unpredictability In The Art
`Of Formulating Dermal Fillers ............................................................. 4
`1.
`Physical And Rheological Properties Must Be Accounted
`For .............................................................................................. 5
`HA Properties Affect Product Properties ................................... 6
`Crosslinkers, And The Degree Of Crosslinking, Impact
`The Physical And Rheological Properties ................................. 7
`Crosslinking Processes Introduce Additional Variables ............ 9
`Gels Differ Between Monophasic And Biphasic ..................... 10
`Post-Crosslinking Steps Further Complicate The Process ...... 11
`Degradation From Heat Sterilization Also Creates
`Concerns ................................................................................... 12
`Including Lidocaine Added Complexity And Uncertainty ...... 13
`8.
`The ’519 Patent .................................................................................. 15
`B.
`III. PERSON OF ORDINARY SKILL IN THE ART ....................................... 17
`IV. CLAIM CONSTRUCTION ......................................................................... 19
`V.
`PETITIONER’S ASSERTED REFERENCES ............................................ 20
`A.
`P050047/S005 .................................................................................... 20
`B. Weinkle............................................................................................... 21
`C. U.S. 2010/0028438 ............................................................................. 21
`D.
`Lebreton .............................................................................................. 22
`E.
`Sadozai ............................................................................................... 22
`F.
`P050047 .............................................................................................. 24
`G. Kinney ................................................................................................ 24
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`IPR2020-00084
`Patent 9,089,519
`
`TABLE OF CONTENTS
`VI. THE PETITION IS PREMISED ON UNSUPPORTED EXPERT
`OPINION THAT MISCHARACTERIZES THE STATE OF THE
`ART AND DISPARAGES DR. LEBRETON’S DECLARATION
`WITHOUT BASIS ....................................................................................... 25
`A. Dr. DeVore Offers Opinions He Is Unable To Defend Based On
`Credentials He Does Not Have .......................................................... 25
`1.
`Dr. DeVore Concedes The Art Is Complex, Contrary To
`His Declaration’s Claims of “Simplicity” ............................... 25
`Dr. DeVore Applied Hindsight ................................................ 27
`2.
`Dr. DeVore Cannot Or Will Not Explain The Chemistry ....... 28
`3.
`Dr. DeVore Misrepresented His Credentials ........................... 29
`4.
`B. Dr. DeVore’s Disparagement Of Dr. Lebreton’s Declaration Is
`Unfounded .......................................................................................... 31
`VII. CLAIMS 1-4 ARE NOT ANTICIPATED (GROUNDS 1-3)...................... 34
`A.
`Claims 1-4 Pre-Date Petitioner’s Asserted Art .................................. 35
`1.
`The Provisional Applications Adequately Describe
`Claims 1-4 ................................................................................ 35
`The Provisional Applications Disclose Sufficient Species
`To Support The Claims ............................................................ 37
`The ’884 Application Provides Adequate Disclosure ............. 38
`3.
`Claims 1-4 Are Not Anticipated By P050047/S005 (Ground 1)
`Or Weinkle (Ground 2) ...................................................................... 39
`1.
`Petitioner Has Not Proven P050047/S005 Is Prior Art ........... 39
`2.
`P050047/S005 Does Not Anticipate (Ground 1) ..................... 40
`3. Weinkle Does Not Anticipate (Ground 2) ............................... 41
`VIII. CLAIMS 1-8 WOULD NOT HAVE BEEN OBVIOUS OVER
`LEBRETON IN VIEW OF SADOZAI (GROUND 4) ................................ 41
`A.
`The POSA Would Not Have Been Motivated To Combine
`Lebreton’s BDDE-Crosslinked Filler With Sadozai’s Use Of
`Lidocaine In Its pBCDI-Crosslinked Filler ........................................ 41
`
`B.
`
`2.
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`IPR2020-00084
`Patent 9,089,519
`
`B.
`
`C.
`
`D.
`
`C.
`
`D.
`
`2.
`
`3.
`
`2.
`
`3.
`
`TABLE OF CONTENTS
`The POSA Would Have Been Further Discouraged By
`Lebreton’s And Sadozai’s Incompatible Processes ........................... 46
`The POSA Would Have Had No Reasonable Expectation Of
`Success In Combining Lebreton And Sadozai ................................... 49
`Lebreton and Sadozai Fail To Teach The Limitations Of Claims
`1-8 ....................................................................................................... 51
`1.
`It Would Not Have Been Obvious That A First BDDE-
`Crosslinked HA Filler Containing Lidocaine Would
`Have Performed Substantially The Same As An
`Otherwise Identical Composition Without Lidocaine ............. 51
`Lidocaine “Freely Released In Vivo” Would Not Have
`Been Obvious (Claims 2, 4, 8) ................................................. 53
`Claims 5-7: The Stability Limitations Would Not Have
`Been Obvious ........................................................................... 57
`IX. CLAIMS 1-8 WOULD NOT HAVE BEEN OBVIOUS OVER
`P050047 IN VIEW OF KINNEY (GROUND 5) ......................................... 59
`A.
`Petitioner Has Not Proven P050047 Is Prior Art ............................... 59
`B.
`The POSA Would Not Have Been Motivated To Combine
`P050047 And Kinney ......................................................................... 60
`The POSA Would Not Have Had A Reasonable Expectation Of
`Success For Adding Lidocaine ........................................................... 61
`Petitioner’s Combination Does Not Teach The Claim
`Limitations .......................................................................................... 65
`1.
`It Would Not Have Been Obvious That A BDDE-
`Crosslinked HA Dermal Filler Containing Lidocaine
`Would Have Performed Substantially The Same As An
`Otherwise Identical Composition Without Lidocaine ............. 65
`Claims 2, 4, 8: Lidocaine “Freely Released In Vivo”
`Would Not Have Been Obvious .............................................. 66
`Claims 5-7: The Stability Limitations Would Not Have
`Been Obvious ........................................................................... 67
`CONCLUSION ............................................................................................. 69
`
`X.
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`IPR2020-00084
`Patent 9,089,519
`
`EXHIBIT LIST
`
`Exhibit No.
`2001
`2002
`2003
`2004
`
`2005
`2006
`2007
`2008
`2009
`2010
`2011
`
`2012
`
`2013
`2014
`2015
`
`2016
`
`2017
`
`2018
`
`Exhibit Description
`Juvéderm Ultra™ XC Label
`Juvéderm Ultra Plus™ XC Label
`Juvéderm Voluma®XC Label
`U.S. Patent Publication No. 2004/0101959 to Marko et al,
`published May 27, 2004
`Excerpts from U.S. 8,822,676 file history
`Excerpts from U.S. 9,089,519 file history
`About Juvéderm Ultra Plus™ XC
`About Juvéderm Volbella® XC
`About Juvéderm Voluma® XC
`Reserved
`Declaration in support of unopposed motion for pro hac vice
`admission of Elizabeth Flanagan
`Updated Declaration in support of unopposed motion for pro hac
`vice admission of Elizabeth Flanagan
`Declaration of Cory J. Berkland, Ph.D
`Curriculum Vitae, Cory J. Berkland, Ph.D.
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`Chs. 1-6, 2006. (“Kuo”)
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`Vol. 15, 1982; 386-395. (“Cleland”)
`Knill, et al., Effect of Metal Ions on the Rheological Flow Profiles
`of Hyaluronate Solutions, Kennedy Ch. 21, Hyaluronan, 2002;
`175-180. (“Knill”)
`
`
`
`-iv-
`
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`
`

`

`Exhibit No.
`2019
`
`2020
`2021
`
`2022
`
`2023
`
`2024
`2025
`2026
`
`2027
`
`2028
`
`2029
`
`2030
`
`IPR2020-00084
`Patent 9,089,519
`
`Exhibit Description
`Kablik, et al., Comparative Physical Properties of Hyaluronic
`Acid Dermal Fillers, Dermatologic Surgery, Vol. 35, 2009; 302-
`312. (“Kablik”)
`Reserved
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`2684. (“Lapcik”)
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`(“Matsumoto”)
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`Reserved
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`Hydrophilic Network and Evaluation of Its Potential For
`Controlled Release of Agrochemicals, Reactive & Functional
`Polymers, Vol. 53, 2002; 125-141. (“Bajpai”)
`Ghosh, et al., Rheological Characterization of in Situ Cross-
`Linkable Hyaluronan Hydrogels, Biomacromolecules, Vol. 6,
`2005; 2857-2865. (“Ghosh”)
`Leach and Schmidt, Hyaluronan; Encyclopedia of Biomaterials
`and Biomedical Engineering, 2004; 779-789. (“Leach”)
`Wik, Rheology of Hyaluronan Products, Kennedy Ch. 24,
`Hyaluronan, 2002; 201-204. (“Wik”)
`Scott and Heatley, Biological Properties of Hyaluronan are
`Controlled and Sequestered by Tertiary Structures, Kennedy Ch.
`15, Hyaluronan, 2002; 117-122. (“Scott”)
`
`
`
`-v-
`
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`

`

`Exhibit No.
`2031
`
`2032
`
`2033
`
`2034
`
`2035
`
`2036
`
`2037
`
`2038
`
`2039
`
`2040
`
`IPR2020-00084
`Patent 9,089,519
`
`Exhibit Description
`Mo, et al., Effects of Sodium Chloride, Guanidine Hydrochloride,
`and Sucrose on the Viscoelastic Properties of Sodium Hyaluronate
`Solutions, Biopolymers, Vol. 50, 1999; 23-34. (“Mo”)
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`(“Lefebvre”)
`Hoefling, et al., Rheological Creep Experiments Utilizing Mixtures
`of 1% Hylan A Solution and 0.5% Hylan B Gel Slurry, Kennedy
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`1998; 1-6. (“Bailey”)
`Ege, Organic Chemistry Structure and Reactivity, 3rd Ed., 1994;
`530. (“Ege”)
`Inoue and Nagasawa, Preparation, by Chemical Degradation of
`Hyaluronic Acid, of a Series of Even- and Odd-Numbered
`Oligosaccharides Having A 2-Acetamido-2-Deoxy-D-Glucose and
`A D-Glucuronic Acid Residue, Respectively, at the Reducing End,
`Carbohydrate Research, Vol. 141, 1985; 99-110. (“Inoue”)
`Tokita and Okamoto, Degradation of Hyaluronic Acid-Kinetic
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`No. 8, 1996; 1011-1014. (“Tokita 1996”)
`Tokita and Okamoto, Hydrolytic Degradation of Hyaluronic Acid,
`Polymer Degradation and Stability, Vol. 48, 1995; 269-273.
`(“Tokita 1995”)
`Tømmeraas and Melander, Kinetics of Hyaluronan Hydrolysis in
`Acidic Solution at Various pH Values, Biomacromolecules, Vol. 9,
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`Lowry and Beavers, Thermal Stability of Sodium Hyaluronate in
`Aqueous Solution, Journal of Biomedical Materials Research, Vol.
`28, 1994; 1239-1244. (“Lowry”)
`
`
`
`-vi-
`
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`

`Exhibit No.
`2041
`
`2042
`
`2043
`
`2044
`
`2045
`2046
`2047
`
`2048
`2049
`
`2050
`2051
`
`2052
`
`IPR2020-00084
`Patent 9,089,519
`
`Exhibit Description
`Bothner, et al., Limiting Viscosity Number and Weight Average
`Molecular Weight of Hyaluronate Samples Produced by Heat
`Degradation, International Journal of Biological Macromolecules,
`Vol. 10, 1988; 287-291. (“Bothner”)
`Powell, Stability of Lidocaine in Aqueous Solution: Effect of
`Temperature, pH, Buffer, and Metal Ions on Amide Hydrolysis,
`Pharmaceutical Research, Vol. 4, No. 1, 1987; 42-45. (“Powell”)
`The Merck Index, An Encyclopedia of Chemicals, Drugs, and
`Biologicals, 12th Ed., 1996; 936-937. (“1996 Merck Index:
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`Bromage, A Comparison of the Hydrochloride and Carbon
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`Osteoarthritis, Biomaterials, Vol. 23, 2002; 4503-4513.
`(“Barbucci”)
`Reserved
`Brandt and Cazzaniga, Hyaluronic Acid Fillers: Restylane and
`Perlane, Facial Plastic Surgery Clinics of North America, Vol. 15,
`2007; 63-76. (“Brandt”)
`Declaration of Amelia E. Murray.
`Zhao, et al., Synthesis and Characterization of A Novel Double
`Crosslinked Hyaluronan Hydrogel, Journal of Materials Science:
`Materials in Medicine, Vol. 13, 2002; 11-16. (“Zhao”)
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`Juvéderm® XC, Clinical, Cosmetic and Investigational
`Dermatology, Vol. 6, 2013; 183-189. (“Ballin”)
`
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`IPR2020-00084
`Patent 9,089,519
`
`Exhibit Description
`
`Exhibit No.
`2053-2054 Reserved
`2055
`Khabarov, et al., Chemical Modifications, Solid Phase, Radio-
`Chemical and Enzymatic Transformations of Hyaluronic Acid,
`Polyak Ch. 5, Hyaluronic Acid: Preparation, Properties,
`Application in Biology and Medicine, 1st Ed., 2015; 121-141.
`(“Khabarov”)
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`Dermatology, Vol. 17, No. 9, 2018; 948-954. (“Micheels 2018”)
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`Hyaluronic Acid Dermal Fillers, Journal of Drugs in
`Dermatology, Vol. 10, No. 9, 2011; 974-980. (“Stocks”)
`Shah and Barnett, Hyaluronic Acid Gels, Harland and
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`and Pain Reduction, Journal of Drugs in Dermatology, Vol. 8, No.
`10, 2009; s21-s23. (“Busso 2009”)
`
`2056
`
`2057
`
`2058
`2059
`
`2060
`
`2061
`
`2062
`
`2063
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`
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`Exhibit No.
`2064
`
`2065
`2066
`2067
`2068
`
`2069
`2070
`
`2071
`
`2072
`
`2073
`2074
`
`2075
`
`IPR2020-00084
`Patent 9,089,519
`
`Exhibit Description
`Busso and Voigts, An Investigation of Changes in Physical
`Properties of Injectable Calcium Hydroxylapatite in a Carrier Gel
`when Mixed with Lidocaine and with Lidocaine/Epinepherine,
`Dermatologic Surgery, Vol. 34, 2008; s16-s24. (“Busso 2008”)
`Reserved
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`Reserved
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`(“Liao”)
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`rtes-Medical-Initiates-Market-Launch-Commercial-Sale.
`
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`IPR2020-00084
`Patent 9,089,519
`
`Exhibit Description
`
`Exhibit No.
`2076-2077 Reserved
`2078
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`https://www.fda.gov/regulatory-information/search-fda-guidance-
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`Acid Hydrogels, Journal of Controlled Release, Vol. 120, No. 3,
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`Reserved
`Vivacy Laboratories Testing Report on FR0857575, with
`translation,
`https://register.epo.org/application?documentId=ER83XYVA8475
`754&number=EP09768146&lng=fr&npl=true.
`Vivacy Laboratories Testing Report on EP2 349 203 B1, with
`translation,
`https://register.epo.org/application?documentId=EWD1Y85G8021
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`2079
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`2080
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`2081
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`2083
`
`2084
`
`2085
`
`2086
`2087
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`Exhibit No.
`2088
`
`IPR2020-00084
`Patent 9,089,519
`
`Exhibit Description
`Kuroda, et al., Interactions Between Local Anesthetics and Na+
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`205. (“Anslyn”)
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`2095-2099 Reserved
`2100
`Transcript of the Deposition of Dale DeVore
`2101-2104 Reserved
`
`2089
`
`2090
`
`2091
`
`2092
`
`2093
`
`2094
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`IPR2020-00084
`Patent 9,089,519
`
`Exhibit No.
`2105
`
`2106
`
`2123
`
`Exhibit Description
`Anika Therapeutics, Inc., SEC Form 10-k, 2006,
`https://www.sec.gov/Archives/edgar/data/898437/0001104659070
`18715/0001104659-07-018715-index.htm. (Ex. 05 to DeVore
`Dep.)
`FDA Premarket Approval, CTA Suppl. 004,
`https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cf
`m?id=P050033S004. (Ex. 06 to DeVore Dep.)
`2107-2121 Reserved
`2122
`FDA Premarket Approval, CTA Suppl. 001. (Ex. 22 to DeVore
`Dep.)
`FDA Premarket Approval, CTA Suppl. 003,
`https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cf
`m?id=P050033S001. (Ex. 23 to DeVore Dep.)
`2124-2127 Reserved
`2128
`U.S. Pat. No. 9,352,046 (DeVore). (Ex. 28 to DeVore Dep.)
`2129
`ESM Technologies, Inc. v BIOVA, LLC and Matthew Stegenga,
`C.A. No. 6:10-cv-03009-RED (W.D. Mo. 2011), Declaration of
`Dale Paul DeVore, Ph.D. (Ex. 29 to DeVore Dep.)
`Curriculum Vitae of Dale P. DeVore, Ph.D, submitted in Biocell
`Technology, LLC v. ARTHRO-7 INC., C.A. No. 8:12-cv-00516-
`JVS-RNB (C.D. Ca. Mar. 25, 2013). (Ex. 30 to DeVore Dep.)
`2131-2134 Reserved
`2135
`Mentor Corporation, Press Release and Third Quarter Financial
`Results, 2006,
`https://www.sec.gov/Archives/edgar/data/64892/00000648920600
`0005/k8feb0606results.htm. (Ex. 35 to DeVore Dep.)
`Mentor Corporation, SEC Form 10-Q, 2006,
`https://www.sec.gov/Archives/edgar/data/64892/00010032970600
`0047/0001003297-06-000047-index.htm. (Ex. 36 to DeVore Dep.)
`
`2130
`
`2136
`
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`IPR2020-00084
`Patent 9,089,519
`
`Exhibit No.
`2137
`
`2138
`
`2139
`
`2140
`
`Exhibit Description
`Mentor Corporation, SEC Form 10-K, 2006,
`https://www.sec.gov/Archives/edgar/data/64892/00000648920600
`0023/0000064892-06-000023-index.htm. (Ex. 37 to DeVore Dep.)
`Mentor Corporation, SEC Form 10-K, 2007,
`https://www.sec.gov/Archives/edgar/data/64892/00013623100700
`0951/0001362310-07-000951-index.htm. (Ex. 38 to DeVore
`Dep.)
`Mentor Corporation, SEC Form 10-K, 2008,
`https://www.sec.gov/Archives/edgar/data/64892/00013623100800
`3062/0001362310-08-003062-index.htm. (Ex. 39 to DeVore Dep.)
`Identification of Expert Witness in International Trade
`Commission Inv. No. 337-TA-515 (2004). (Ex. 40 to DeVore
`Dep.)
`2141-2147 Reserved
`2148
`Silver, et al., Viscoelastic Evaluation of Different Hyaluronic Acid
`Based Fillers Using Vibrational Optical Coherence Tomography,
`Materials Sciences and Applications, Vol. 10, 2019; 423-431. (Ex.
`48 to DeVore Dep.)
`Pendant Modification Figure. (Ex. 49 to DeVore Dep.)
`2149
`2150-2151 Reserved
`2152
`Figure Depicting Chemical Structure of DEO. (Ex. 52 to DeVore
`Dep.)
`Figure Depicting Chemical Structure of BDDE. (Ex. 53 to DeVore
`Dep.)
`Figure Depicting Chemical Structure of DVS. (Ex. 54 to DeVore
`Dep.)
`Figure Depicting Incorrect Chemical Structure of pBCDI. (Ex. 55
`to DeVore Dep.)
`Figure Depicting Correct Chemical Structure of pBCDI. (Ex. 56 to
`DeVore Dep.)
`
`2153
`
`2154
`
`2155
`
`2156
`
`
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`IPR2020-00084
`Patent 9,089,519
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`Exhibit Description
`
`Exhibit No.
`2157
`2158
`
`Reserved
`Figure Depicting Chemical Structure of NaHA. (Ex. 58 to DeVore
`Dep.)
`2159-2164 Reserved
`2165
`Lidocaine Quiz. (Ex. 65 to DeVore Dep.)
`2166-2171 Reserved
`2172
`Declaration of Dale P. DeVore in U.S. Patent Application No.
`13/813,557. (Ex. 72 to DeVore Dep.)
`Declaration of Dale P. Devore in U.S. Patent Application No.
`14/430,741. (Ex. 73 to DeVore Dep.)
`Figures Depicting Chemical Structures of Crosslinked HA. (Ex. 74
`to DeVore Dep.)
`
`2173
`
`2174
`
`
`
`
`
`
`
`
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`IPR2020-00084
`Patent 9,089,519
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`
`
`
`Abbreviation
`’519 patent
`BDDE
`BCDI
`DEO
`DVS
`Challenged
`Claims
`Challenged
`Patents
`
`ID
`HA
`pBCDI
`Pet.
`POSA
`Provisional
`Applications
`
`TABLE OF ABBREVIATIONS
`
`Term
`
`U.S. Patent No. 9,089,519
`butanediol diglycidyl ether
`class of crosslinkers made using biscarbodiimide derivatives
`1,2,7,8-diepoxyoctane
`divinyl sulfone
`Claims 1-8 of U.S. Patent No. 9,089,519
`
`U.S. Patent Nos. 8,450,475; 8,357,795; 9,238,013; 9,358,322;
`8,822,676; and 9,089,519, challenged in one or more of
`IPR2019-01505, IPR2019-01506, IPR2019-01508, IPR2019-
`01509, IPR2019-01617, IPR2019-01632, and IPR2020-00084
`Institution Decision, Paper 12
`hyaluronic acid
`p-phenylene-bis(ethylcarbodiimide)
`Petition, Paper 1
`Person of Ordinary Skill in the Art
`Provisional Application No. 61/085,956, filed August 4, 2008
`(EX1013); Provisional Application No. 61/087,934, filed
`August 11, 2008) (EX1028); and Provisional Application No.
`61/096,278, filed September 11, 2008 (EX1044)
`
`
`All emphasis in this Patent Owner Response is added unless otherwise noted.
`
`
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`IPR2020-00084
`Patent 9,089,519
`
`I.
`
`
`INTRODUCTION
`Formulating dermal fillers is complex. On the one hand, the filler needs to
`
`be easily injectable through a very small needle into a patient’s most delicate facial
`
`features. On the other, it needs to be sufficiently bulky, viscous, and hydrophilic to
`
`actually fill or plump skin. All of this must be accomplished in a stable, sterile,
`
`long-lasting, non-allergic, and biocompatible composition. By the mid-2000s, the
`
`field accomplished these goals using crosslinked hyaluronic acid (“HA”) gels. But
`
`inventing each new filler was a formidable task. And if the POSA were to
`
`consider incorporating lidocaine to mitigate pain injection, as Petitioner suggests,
`
`that would further complicate the chemistry. Achieving the delicate balance of
`
`properties in HA gels must overcome numerous complications with unpredictable
`
`results from changes big and small.
`
`
`
`Despite these challenges, Dr. Pierre Lebreton invented formulations that an
`
`ordinary artisan would not have reasonably expected to succeed: stable, sterile
`
`dermal filler compositions comprising BDDE-crosslinked HA and lidocaine, where
`
`the lidocaine freely releases in vivo. The Challenged Patents claim these
`
`formulations. Allergan sells these fillers (and non-lidocaine fillers) as part of its
`
`successful “JUVÉDERM®” product line.
`
`
`
`
`
`If the parties’ briefs appear as ships passing in the night, they are. From
`
`stem to stern, the Petition disregards scientific evidence of the state of the art,
`
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`IPR2020-00084
`Patent 9,089,519
`offering instead a fiction in which vastly different dermal fillers are easily divisible
`
`compositions with discrete pieces that can be easily mixed in or switched out.
`
`Petitioner uses this fiction to claim “[t]here is no credible reason why the POSITA
`
`would have not expected that lidocaine could be successfully incorporated into a
`
`BDDE-crosslinked gel,” Pet. 37, and to cast doubt on the Patent Office’s allowance
`
`of the Challenged Claims after Dr. Lebreton defended his inventions based on the
`
`state of the art. As Allergan here shows, Petitioner’s narrative is false.
`
`
`
`Petitioner relies on the opinions of its “expert,” Dr. Dale DeVore; the Board
`
`did likewise in instituting. ID 44-50. But contemporaneous patents and
`
`publications refute Petitioner’s and Dr. DeVore’s account and confirm that of
`
`Dr. Lebreton, a chemist who, for over 25 years before his death in 2019, designed
`
`filler formulations and was intimately familiar with their difficulties and
`
`complexities. EX2081. Indeed, when seeking his own contemporaneous patent,
`
`Dr. DeVore acknowledged to the Patent Office that developing dermal fillers is a
`
`“formidable task.” Only here, as a hired expert, does Dr. DeVore oversimplify the
`
`art and use hindsight reconstruction—violating his purpose of assisting the Board,
`
`and cardinal rules of obviousness.
`
`
`
`Petitioner’s hindsight-based, outcome-oriented approach could not be any
`
`clearer than when Dr. DeVore’s opinions were tested, as welcomed by the Board.
`
`During cross-examination, Dr. DeVore acknowledged:
`
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`IPR2020-00084
`Patent 9,089,519
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`• he does not actually agree with his or Petitioner’s statements
`
`regarding the purported ease of the art;
`
`• his opinions rely on textbook hindsight analysis;
`
`• he struggles to understand the relevant chemistry; and
`
`• he misrepresented his credentials.
`
`
`
`Further, in addition to this new information about Dr. DeVore’s opinions,
`
`the Board also now has before it the opinions of Dr. Cory Berkland. Dr. Berkland,
`
`a Professor of Pharmaceutical Chemistry at the University of Kansas, has spent
`
`years researching and publishing on chemical modifications of HA for
`
`pharmaceutical and biomaterials applications. EX2013, ¶¶ 3, 7. Unlike Dr.
`
`DeVore’s, Dr. Berkland’s opinions are supported by the references he reviewed
`
`and discusses in detail.
`
`For all the reasons detailed herein, each ground lacks merit. As the Board
`
`already recognized, all Challenged Claims are entitled to priority as of April 4,
`
`2008, or—at worst—February 26, 2009. Grounds 1-3 rely on later art. Grounds
`
`4-5 rely on Petitioner’s unsupported oversimplification of the art. Petitioner’s first
`
`principal combination—the Lebreton and Sadozai references—seeks to combine
`
`Lebreton’s BDDE-crosslinked HA without lidocaine with Sadozai’s BCDI-
`
`crosslinked HA, even though Sadozai specifically teaches against using other
`
`crosslinked HA besides BCDI. Petitioner’s second principal combination—
`
`
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`Patent 9,089,519
`P050047 and Kinney—likewise oversimplifies, again seeking to just swap one
`
`crosslinker for another without considering the underlying chemistry. Only with
`
`improper hindsight and selective citations can Petitioner support its narrative. The
`
`Board should reject all grounds and uphold the Challenged Claims.
`
`II. BACKGROUND
`A. The POSA Faced Intricacies And Unpredictability In The Art Of
`Formulating Dermal Fillers
`Broadly speaking, the Challenged Patents relate to crosslinked-HA dermal
`
`fillers, with a priority date of August 4, 2008. HA, a naturally occurring substance
`
`in the body, has a unique ability to retain water and thereby plump up skin when
`
`used as an injectable filler. “Free HA”—a solution of HA and water—rapidly
`
`dissipates or degrades upon injection. EX1045, 36-37; EX1056, 537-538, 543-
`
`544, 551. Accordingly, HA is strengthened by “crosslinking” it with reagents
`
`(“crosslinkers”) that bond together the HA polymer chains, creating a gel-like
`
`composition. EX1045, 36-37; EX2068, 41-46, 49; EX2079, 156.
`
`To formulate a usable crosslinked HA filler, the artisan faced numerous
`
`additional considerations, each of which could affect whether the formulation
`
`would actually work as a dermal filler and what its physical and rheological
`
`properties might be. Despite Petitioner’s arguments, this point is not genuinely
`
`disputed. Outside the context of this litigation, in his own contemporaneously filed
`
`patent, Dr. DeVore acknowledges that design of dermal fillers is a “formidable
`
`
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`Patent 9,089,519
`task” due to the almost infinite number of combinations of “many complex
`
`factors.” EX2128, 6:30-36.
`
`As discussed below, some of these considerations conflict—such as having a
`
`consistency viscous enough to fill in wrinkles, but fluid enough to permit
`
`administration by syringe with relatively low injection pressure, through a
`
`relatively small needle (to limit pain at the injection site). As further discussed
`
`below, it is also important that the formulation remain stable on the shelf and after
`
`injection, to minimize the frequency of repeated injections, and avoid allergic
`
`reactions.
`
`1.
`
`Physical And Rheological Properties Must Be Accounted
`For
`The performance considerations for an HA-based dermal filler manifest as
`
`numerous physical and rheological properties, such as the gel’s “swelling”
`
`capacity, viscosity, extrusion force, hardness, shelf life, stability, and sterility.
`
`Swelling capacity, for example, is the ability of HA to bind large volumes of water
`
`causing it to swell, which results in creating volume and lift for wrinkle filling.
`
`Viscosity and, similarly, extrusion force relate to the ease with which the filler can
`
`be injected into the skin through a narrow syringe needle. EX1045, 40-41. Gel
`
`hardness refers to the stiffness and deformation resistance of a gel, and is measured
`
`as G′ (elastic or storage modulus). EX1045, 38-39. A gel’s hardness relates to the
`
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`force required to inject the product into a patient’s skin and the ability of the filler
`
`to provide lift and support. EX104