UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`PROLLENIUM US INC.,
`Petitioner
`
`v.
`
`ALLERGAN INDUSTRIE, SAS,
`Patent Owner
`
`IPR2019-01505, Patent 8,450,475 B2
`IPR2019-01506, Patent 8,357,795 B2
`IPR2019-01508, Patent 9,238,013 B2
`IPR2019-01509, Patent 9,358,322 B2
`IPR2019-01617, Patent 8,822,676 B2
`IPR2019-01632, Patent 8,357,795 B2
`IPR2020-00084, Patent 9,089,519 B2
`
`DECLARATION OF CORY J. BERKLAND, PH.D.
`
`ALL 2013
`PROLLENIUM V. ALLERGAN
`IPR2019-01505 et al.
`
`

`

`TABLE OF CONTENTS
`
`Page
`
`
`
`EXPERIENCE AND QUALIFICATIONS .................................................... 2 
`SUMMARY OF OPINIONS .......................................................................... 6 
` PERSON OF ORDINARY SKILL IN THE ART ....................................... 14 
` TECHNICAL BACKGROUND: HA’S PROPERTIES AND THE
`COMPLEXITIES OF DESIGNING INJECTABLE DERMAL
`FILLERS ....................................................................................................... 16 
`HA Is a Prevalent Natural Biopolymer .............................................. 18 
`A.
`B.
`The Chemical Structure of HA ........................................................... 19 
`Aqueous Solutions of HA Have Complex Physical Properties ......... 22 
`C.
`D.
`Chemically Modified HA Is Used in Dermal and Soft Tissue
`HA Fillers To Impart Desirable Filler Properties .............................. 28 
`The Complexity of Designing HA Dermal and Soft Tissue
`Fillers .................................................................................................. 33 
`Crosslinking affects the rheological properties of HA
`1.
`compositions ............................................................................ 36 
`Non-covalent HA interactions affect the rheological
`properties of HA compositions ................................................ 56 
`Post-crosslinking processing affects the rheological
`properties of HA compositions ................................................ 61 
`Chemical degradation of HA involves several complex
`mechanisms affected by many variables, and can lead to
`deterioration of rheological characteristics .............................. 67 
`F.
`Chemical Degradation of HA Compositions by Lidocaine HCl ....... 71 
` DISCUSSION OF THE ASSERTED ART ................................................. 76 
`A.
`Lebreton (Ex. 1029) ........................................................................... 76 
`B.
`Sadozai (Ex. 1030) ............................................................................. 78 
`C.
`Zhao (Ex. 1058) .................................................................................. 85 
`D. Kinney (Ex. 1012) .............................................................................. 88 
`E.
`Reinmuller (Ex. 1059) ........................................................................ 92 
`
`E.
`
`2.
`
`3.
`
`4.
`
`-i-
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`

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`TABLE OF CONTENTS
`(continued)
`
`Page
`
`2.
`
`F. Monheit (Ex. 1022) ............................................................................ 97 
`G. Narins (Ex. 1007) ............................................................................... 98 
`H.
`Clark (Ex. 1008) ................................................................................. 99 
`I.
`Smith (Ex. 1009) .............................................................................. 101 
`J.
`CTA Summary (Ex. 1050) and Purported Draft CTA Package
`Insert (Ex. 1031) ............................................................................... 103 
`P050047 (Ex. 1074) .......................................................................... 106 
`K.
` OVERVIEW OF THE CHALLENGED PATENT CLAIMS ................... 107 
`A.
`The Challenged Patents and Claims ................................................. 107 
`B.
`The Lebreton Declaration ................................................................. 111 
`1.
`Dr. Lebreton’s Declaration Reflected Well-Established
`Properties of HA and Lidocaine ............................................ 111 
`The Patent Examples Demonstrate Dr. Lebreton’s
`Invention ................................................................................ 115 
` CLAIM CONSTRUCTION OPINIONS .................................................... 129 
` ANALYSIS OF GROUNDS ...................................................................... 137 
`A.
`LEBRETON AND SADOZAI (ALONE OR WITH
`ADDITIONAL REFERENCES) WOULD NOT HAVE
`REASONABLY LED A SKILLED ARTISAN TO ACHIEVE
`THE CLAIMED FILLERS .............................................................. 138 
`1.
`Usable BDDE-Crosslinked HA Fillers Containing
`Lidocaine ................................................................................ 138 
`Unbound/Freely Released Lidocaine ..................................... 157 
`Heat-Sterilized BDDE-Crosslinked HA Fillers ..................... 162 
`Filler Properties Maintained During Storage ......................... 164 
`Presence and Amount of Uncrosslinked, Soluble, or Free
`HA .......................................................................................... 169 
`Cohesivity .............................................................................. 172 
`Presence and Size of BDDE-Crosslinked HA Particles ........ 174 
`
`2.
`3.
`4.
`5.
`
`6.
`7.
`
`-ii-
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`

`

`TABLE OF CONTENTS
`(continued)
`
`Page
`
`2.
`3.
`4.
`5.
`
`C.
`
`Degree of Crosslinking .......................................................... 176 
`8.
`pH ........................................................................................... 179 
`9.
`B. KINNEY AND ZHAO (ALONE OR WITH ADDITIONAL
`REFERENCES) WOULD NOT HAVE REASONABLY LED
`A SKILLED ARTISAN TO ACHIEVE THE CLAIMED
`FILLERS .......................................................................................... 181 
`1.
`Usable BDDE Double-Crosslinked HA Fillers
`Containing Lidocaine ............................................................. 181 
`Unbound/Freely Released Lidocaine ..................................... 189 
`Heat-Sterilized BDDE Double-Crosslinked HA Fillers ........ 193 
`Filler Properties Maintained During Storage ......................... 197 
`Presence and Amount of Uncrosslinked, Soluble, or Free
`HA .......................................................................................... 202 
`Presence and Size of BDDE-Crosslinked HA Particles ........ 205 
`6.
`Degree of crosslinking ........................................................... 207 
`7.
`pH ........................................................................................... 210 
`8.
`REINMULLER AND LEBRETON (ALONE OR WITH
`ADDITIONAL REFERENCES) WOULD NOT HAVE
`REASONABLY LED A SKILLED ARTISAN TO ACHIEVE
`THE CLAIMED FILLERS .............................................................. 212 
`1.
`Usable BDDE Crosslinked HA Fillers Containing
`Lidocaine ................................................................................ 212 
`Heat-Sterilized BDDE Double-Crosslinked HA Fillers ........ 229 
`Filler Properties Maintained During Storage ......................... 231 
`Presence and Amount of Uncrosslinked, Soluble, or Free
`HA .......................................................................................... 235 
`Unbound/Freely Released Lidocaine ..................................... 238 
`Degree of Crosslinking .......................................................... 240 
`pH ........................................................................................... 243 
`
`2.
`3.
`4.
`
`5.
`6.
`7.
`
`-iii-
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`

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`
`
`D.
`
`E.
`
`TABLE OF CONTENTS
`(continued)
`
`Page
`
`THE CTA SUMMARY WOULD NOT HAVE
`REASONABLY LED A SKILLED ARTISAN TO ACHIEVE
`THE CLAIMED FILLERS .............................................................. 245 
`P050047 AND KINNEY WOULD NOT HAVE
`REASONABLY LED A SKILLED ARTISAN TO ACHIEVE
`THE CLAIMED FILLERS .............................................................. 252 
`1.
`Usable BDDE Crosslinked HA Fillers Containing
`Lidocaine ................................................................................ 252 
`Unbound/Freely Released Lidocaine ..................................... 256 
`Sterilization of BDDE Crosslinked HA Filler ....................... 258 
`
`2.
`3.
`
`
`
`
`
`-iv-
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`
`I, Cory Berkland, declare as follows:
`
`1.
`
`I have been asked by Jones Day on behalf of Allergan Industrie, SAS
`
`(“Allergan”) to provide this declaration in the matter of the Inter Partes Reviews
`
`of U.S. Patent Nos. 8,357,795 (“’795 patent”), 8,822,676 (“’676 patent”),
`
`9,238,013 (“’013 patent”), 9,089,519 (“’519 patent”), 8,450,475 (“’475 patent”),
`
`and 9,358,322 (“’322 patent”) (the “Challenged Patents”).
`
`2.
`
`I have been asked to review the above-mentioned patents, as well as
`
`the declarations of Dr. Dale DeVore, Petitioner’s expert, submitted with
`
`Petitioner’s Inter Partes Review petitions and the art cited in them. I have also
`
`been asked to provide a discussion of the relevant technology and concepts relating
`
`to the properties of and the design of hyaluronic acid dermal fillers. I have further
`
`been asked to provide my opinions as to whether a person of ordinary skill in the
`
`art as of August 2008 would have been motivated to combine the teachings of the
`
`prior art identified in the Grounds of the Inter Partes Review petitions with a
`
`reasonable expectation of success in achieving dermal fillers possessing the
`
`attributes described in the challenged claims. Finally, I have been asked to review
`
`the cross-examination of Dr. DeVore and to respond to Dr. DeVore’s testimony
`
`where I believe that correction, clarification, or confirmation is warranted.
`
`1
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`

`

`
`
`
`3.
`
`EXPERIENCE AND QUALIFICATIONS
`I am a currently appointed as the Solon E. Summerfield Distinguished
`
`Professor of Pharmaceutical Chemistry and of Chemical and Petroleum
`
`Engineering at The University of Kansas. I also have an appointment in the
`
`Chemistry Department at The University of Kansas that allows me to serve as an
`
`advisor for their graduate students. I also assisted in designing the BioEngineering
`
`Graduate Program at The University of Kansas and I am the former director of the
`
`Biomolecular Engineering track within the BioEngineering Program.
`
`4.
`
`I have been teaching courses for 16 years to undergraduate and
`
`graduate students at The University of Kansas in the areas of pharmaceutical
`
`formulation and drug delivery.
`
`5.
`
`I received a Doctor of Philosophy degree from the University of
`
`Illinois in 2003 and a Master of Science degree from the University of Illinois in
`
`2001, both from the Department of Chemical and Biomolecular Engineering. I
`
`received a Bachelor of Science degree from Iowa State University Department of
`
`Chemical Engineering in 1998.
`
`6.
`
`I have worked in the areas of material science, biomedical
`
`engineering, and pharmaceutical formulation for nearly 20 years. I am experienced
`
`in the practice of biomaterials engineering and pharmaceutical formulation and
`
`drug delivery . I have also published many review and original articles regarding
`
`
`
`2
`
`

`

`
`
`processing, design, and characterization of biomaterials and drug formulations as
`
`set forth in my curriculum vitae. I am familiar with analytical tools and
`
`interpretation of data describing the physical and chemical properties of drugs,
`
`excipients (including polymers), formulations thereof, and biomaterials, such as
`
`the viscoelastic, extrusion force, and drug release properties discussed in this
`
`declaration, and including the effects of storage conditions and sterilization on
`
`such properties.
`
`7. My research involves years of work with hyaluronic acid (HA),
`
`including chemically modifying HA, studying pharmacokinetics and transport of
`
`HA and chemically modified HA, conjugating drugs and peptides to HA,
`
`crosslinking HA, and studying the viscoelastic properties of HA, including as a
`
`function of molecular weight, concentration, and other factors, in crosslinked
`
`systems, and in mixtures with other materials. I have authored approximately 25
`
`peer-reviewed articles on HA-based materials for various biomaterials and
`
`pharmaceutical applications, and in conjunction with these publications and related
`
`work, I have closely studied the properties of HA and the effects of composition,
`
`processing, and other conditions on HA materials.
`
`8.
`
`I have published approximately 185 peer-reviewed papers, and I have
`
`presented my research at many national and international research conferences and
`
`to companies, including more than 80 invited talks. I have given distinguished
`
`
`
`3
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`

`

`
`
`lectures such as the Nagai Foundation Distinguished Lectureship in Japan and a
`
`lectureship at the Center of Excellence in Nanotechnology at the Massachusetts
`
`Institute of Technology. I serve or have served on the editorial advisory board for
`
`a number of peer-reviewed journals: Therapeutic Delivery, The Journal of
`
`Pharmaceutical Sciences, and The Journal of Pharmaceutical Innovation. I also
`
`serve on advisory boards for the Drug Discovery and Development of
`
`Experimental Therapeutics program and the National Institutes of Health
`
`Pharmaceutical Aspects of Biotechnology training grant program at The University
`
`of Kansas.
`
`9.
`
`I have received funding for my research from the National Institutes
`
`of Health, the National Science Foundation, the Department of Defense, the
`
`Department of Energy, the Defense Threat Reduction Agency, the PhRMA
`
`Foundation, the Coulter Foundation, the American Heart Association, the Cystic
`
`Fibrosis Foundation, the Juvenile Diabetes Research Foundation, several other
`
`philanthropic organizations, and multiple pharmaceutical companies.
`
`10.
`
`I am an active participant in a number of professional societies
`
`including the American Institute of Chemical Engineers, the Controlled Release
`
`Society, the American Chemical Society, and the American Association of
`
`Pharmaceutical Scientists. I have also been elected Fellow of the American
`
`Institute for Medical and Biological Engineering and was elected to the National
`
`
`
`4
`
`

`

`
`
`Academy of Inventors. As part of these organizations, I have helped organize and
`
`lead (as a chair or co-chair) scientific sessions, including sessions on drug
`
`formulation and delivery.
`
`11.
`
`I have received numerous awards in recognition of research, including
`
`the Controlled Release Society Young Investigator Award and the Coulter
`
`Translational Research Award. The Controlled Release Society award is given to a
`
`current Controlled Release Society member under the age of 40, who has made
`
`outstanding contributions in the science of controlled release. The Coulter
`
`Translational Research Award is a grant given to researchers who are developing a
`
`product as part of their research. At The University of Kansas, I have received
`
`major research awards such as the University Scholarly Achievement Award, the
`
`Jim Baxendale Commercialization Award, the Leading Light Award, and the
`
`Miller Professional Development Award for Research, and I was named a Bellows
`
`Scholar in the School of Engineering at The University of Kansas. I have also
`
`received the W.T. Kemper Fellowship for teaching excellence at The University of
`
`Kansas.
`
`12.
`
`I have been granted multiple patents and have co-founded four
`
`companies: Orbis Biosciences (sold to Adare Pharmaceuticals), Savara
`
`Pharmaceuticals (NASDAQ: SVRA), Orion BioScience, and Bond Biosciences. I
`
`was the Chief Scientific Officer, a member of the Board of Directors, and Chair of
`
`
`
`5
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`

`
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`the Scientific Advisory Board at Orbis Biosciences. I am also currently the
`
`Chairman of the Board of Directors at Orion BioScience and a Board member at
`
`Bond Biosciences.
`
`13.
`
`I have worked as a consultant in the pharmaceutical industry
`
`providing formulation advice to multiple major pharmaceutical and biotechnology
`
`companies. I have also worked at one of the top Biotechnology investment firms,
`
`Sofinnova Ventures, during a six-month sabbatical in 2014. My consulting work
`
`has included acting as a litigation consultant for Allergan on prior matters related
`
`to the certain of the Challenged Patents, including a prior district court action
`
`challenging the ’475 and ’795 patents, where I was retained as an expert to offer
`
`opinions on the infringement and validity of these patents.
`
`14. A copy of my curriculum vitae, which further details my
`
`qualifications and expertise as well as my publications, is submitted herewith as
`
`Exhibit 2014.
`
`SUMMARY OF OPINIONS
`15.
`In my opinion, for the reasons discussed more specifically throughout
`
`this declaration, an ordinarily skilled artisan would not have been motivated to
`
`combine the disclosures of the prior art identified in Petitioner’s Grounds, nor
`
`would there be any reasonable expectation of success in doing so to achieve dermal
`
`fillers possessing the attributes described in the claims of the Challenged Patents.
`
`
`
`6
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`

`

`
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`16. As explained in Section IV.D below, to be suitable as a dermal filler,
`
`hyaluronic acid (“HA”)-based compositions must balance several key performance
`
`objectives, including (1) remaining in place for a desired amount of time after
`
`injection; (2) providing acceptable volumization and lift; (3) maintaining these
`
`desirable qualities over the shelf life of the filler before injection; and (4) ensuring
`
`injectability of the dermal filler. A skilled artisan in August 2008 would have
`
`appreciated that meeting this combination of objectives with a dermal filler product
`
`would require carefully calibrating a number of compositional and processing
`
`inputs, each of which has an effect on the properties of the dermal filler and can
`
`have effects on each other.
`
`17. Myriad factors affect dermal filler properties. For example, the
`
`rheological properties of HA fillers depend on at least the following compositional
`
`parameters: overall HA concentration, molecular weight and molecular weight
`
`distribution of HA (including free HA concentration), HA source, ionic strength,
`
`osmolarity, pH, degree of swelling, presence of other additives (e.g.,
`
`carboxymethylcellulose, salts, anesthetic, etc.), chemical identity of the
`
`crosslinker(s), and degree of crosslinking (including distribution of resulting
`
`species like pendant crosslinkers). In addition, the rheological properties of HA
`
`fillers are equally, if not more, affected by at least the following processing
`
`parameters: crosslinking reaction conditions (e.g., duration, temperature, pH, ionic
`
`
`
`7
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`

`

`
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`strength, osmolarity, concentration, physical agitation, solvent system(s)), post-
`
`crosslinking processing (e.g., solvent precipitation, dehydrations/drying and
`
`rehydration, particle sizing, physical agitation), sterilization method, and storage
`
`conditions.
`
`18. As discussed in greater detail below, changes to any one of the
`
`compositional or processing parameters just discussed can have an unpredictable,
`
`and profound, effect on the resulting HA dermal filler properties. Dr. DeVore
`
`nicely summarized the situation in his own dermal filler patent: “[s]uch degrees of
`
`freedom are in fact so large and complex that designing the proper implant is a
`
`formidable task.” (Ex. 2128 at 6:30-36.) Because of the delicate interrelationships
`
`between these various parameters and resulting dermal filler properties, a skilled
`
`artisan would recognize that it would not be possible to exchange a component of
`
`one filler composition for a different component of another, without changing its
`
`properties. Dr. DeVore agreed that a skilled artisan would need to test the
`
`resulting composition to characterize the effect of this, and determine the
`
`suitability as a dermal filler product. (Ex. 2100 at 208:8-19 (“You need to conduct
`
`a number of tests to characterize the material.”).) For the same reason, a skilled
`
`artisan could not import new or different features from another composition
`
`without jeopardizing the composition’s properties in unpredictable ways.
`
`
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`8
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`

`

`
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`19. Against this backdrop, Dr. Lebreton attempted to develop novel
`
`dermal fillers that contained the anesthetic lidocaine, to reduce the pain that
`
`patients experience upon injection. As discussed below in Section IV.F, the
`
`information available at the time indicated that lidocaine would destabilize HA
`
`compositions, particularly when combined with autoclave sterilization, resulting in
`
`degradation of the rheological properties necessary for a suitable dermal filler.
`
`Only a very limited number of HA dermal filler products with lidocaine had been
`
`proposed by August 2008, and two of them, Puragen Plus and Elevess, struggled to
`
`reach the U.S. market, including for reasons of instability. And more significantly,
`
`the incorporation of lidocaine into different dermal fillers in no way teaches a
`
`skilled artisan what to expect about its incorporation into a different dermal filler.
`
`Dr. Lebreton found that, despite the expectation that lidocaine would degrade the
`
`HA in a dermal filler composition, it did not have the expected effect of
`
`degradation in his BDDE-crosslinked dermal fillers. He also found that the
`
`resulting dermal filler compositions maintained important properties, such as
`
`viscosity and extrusion force, over extended periods of shelf life, and that they
`
`permitted the free release of lidocaine upon injection. These discoveries are the
`
`basis for the Challenged Patents.
`
`20.
`
`In his Grounds, Dr. DeVore has identified a number of references
`
`forming the basis of his opinions that the claims of the Challenged Patents are
`
`
`
`9
`
`

`

`
`
`obvious. In addition to scientific journal articles, patents, and patent applications,
`
`he also relies on FDA submissions and dermal filler product review articles. In my
`
`opinion, a skilled artisan in formulation research would not routinely review FDA
`
`submissions. In addition, the identification of certain product attributes (such as
`
`HA concentration, particle size, gel hardness, etc.) in a review article would not
`
`teach a skilled artisan how to use such information to achieve the same attributes in
`
`a different composition without also compromising that composition’s suitability
`
`as a dermal filler. Even as to the scientific journal articles and patents, not all of
`
`the publication asserted by Dr. DeVore relate to the dermal filler field.
`
`Accordingly, as discussed in more detail below, it is my opinion that many of Dr.
`
`DeVore’s asserted references are not of the type that a skilled artisan would turn to
`
`in confronting the problem of formulating an HA-based dermal filler. To me, Dr.
`
`DeVore’s testimony that he viewed the claims of the challenged patents as puzzle
`
`pieces, and searched out the puzzle pieces in individual pieces of prior art, was
`
`illuminating in this regard. (Ex. 2100 at 371:24-372:5 (“Q. So if we - - if we think
`
`about the claim like a puzzle with different pieces in it, you went and found each of
`
`the pieces of that puzzle in individual prior art references, right? A. Again, I
`
`believe that’s correct.”).)
`
`21. With respect to the Grounds themselves, the majority of Dr. DeVore’s
`
`arguments are premised on one of three combinations (plus tertiary references to
`
`
`
`10
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`

`

`
`
`supply missing limitations): (1) Lebreton and Sadozai, (2) Kinney and Zhao, and
`
`(3) Reinmuller and Lebreton. For the following reasons, as well as the reasons
`
`described in more detail below in Section VIII, it is my opinion that a skilled
`
`artisan would not have had any motivation to arrive at these particular
`
`combinations, nor would the artisan combine them with any reasonable expectation
`
`of success.
`
`22. Lebreton and Sadozai. Lebreton, while disclosing HA dermal fillers,
`
`does not suggest the addition of lidocaine. Sadozai describes crosslinking with a
`
`class of “BCDI” crosslinkers, to create “water-insoluble, hydrated HA gel
`
`particles,” and discusses the addition of lidocaine. Dr. DeVore suggests modifying
`
`Lebreton by adding the lidocaine described by Sadozai. In my opinion, a skilled
`
`artisan would not have had any motivation to combine disclosures regarding the
`
`soft and free-flowing BDDE-crosslinked gels of Lebreton with those regarding the
`
`densely BCDI-crosslinked particulate-based gels of Sadozai, based on the vastly
`
`different properties (and underlying compositions and processes) of these two gels.
`
`Accordingly, a skilled artisan would not expect the use of lidocaine in Sadozai’s
`
`formulations to be indicative of success in Lebreton’s vastly different
`
`compositions.
`
`23. Kinney and Zhao. Kinney describes observations of a small clinical
`
`study with Puragen Plus, a double-DEO-crosslinked HA dermal filler with
`
`
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`11
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`
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`lidocaine. Zhao describes a “novel” method of double-crosslinking, also primarily
`
`employing DEO, but mentioning BDDE as another possibility. Dr. DeVore
`
`suggests exchanging the DEO crosslinker in Kinney for BDDE, based on Zhao. In
`
`my opinion, a skilled artisan would not be motivated to exchange the DEO in the
`
`Puragen Plus formulation for BDDE, when both references share the common
`
`thread of DEO. In addition, for all of the reasons discussed above about the
`
`unpredictability in doing this exchange, as well as the scarce information provided
`
`about the Puragen Plus composition in Kinney, a skilled artisan would not have a
`
`reasonable expectation of success in doing this. Finally, the fact that Puragen Plus
`
`was never approved in the United States, despite undergoing clinical studies,
`
`would dissuade a skilled artisan from following in Kinney’s path, including the
`
`addition of lidocaine.
`
`24. Reinmuller and Lebreton. Reinmuller describes HA-based
`
`compositions for treating keloids, including a composition with a high amount of
`
`lidocaine. Although Dr. DeVore argues that the HA in Reinmuller is DVS-
`
`crosslinked, I do not believe a skilled artisan would know that with certainty.
`
`Lebreton, as just discussed, describes soft and free-flowing BDDE-crosslinked gels
`
`without lidocaine. Dr. DeVore suggests replacing the Reinmuller crosslinker with
`
`the BDDE of Lebreton. As a preliminary matter, the single composition disclosed
`
`by Reinmuller is not a dermal filler, and has different properties from a dermal
`
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`12
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`
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`filler, and the skilled artisan would not have a clear picture of the nature of the HA
`
`used to prepare it. This alone would dissuade the skilled artisan from using
`
`Reinmuller as a starting point. Additionally, this combination also fails for the
`
`reasons discussed for the prior two combinations: a skilled artisan would not just
`
`exchange a crosslinker and expect success in doing so, and the teachings regarding
`
`particulate-based (according to Dr. DeVore) composition in Reinmuller are
`
`incompatible with Lebreton.
`
`25. Beyond the problems with how Dr. DeVore selected his publications
`
`and then attempted to combine them to arrive at a suitable dermal filler product, his
`
`combinations of these references lack many of the claimed limitations, and in some
`
`cases, teach away from them. To fill these gaps, Dr. DeVore relies on third and
`
`fourth references disclosing yet other different compositions. He then imports
`
`isolated features of these compositions as the missing limitations in his primary
`
`combinations. A skilled artisan would recognize that it would require significant
`
`effort to combine various properties of at least three different compositions and
`
`arrive at the desired dermal filler properties, if it were possible at all. A skilled
`
`artisan would also understand that the mere fact that a particular property exists in
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`a dermal filler product does not mean that it can be translated, intact, to other
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`dermal filler compositions. For all of the reasons discussed in more detail below,
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`the prior art does not supply numerous of the claimed limitations, nor does it teach
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`how to achieve them with a reasonable expectation of success.
` PERSON OF ORDINARY SKILL IN THE ART
`26.
`I understand that the claims of a patent are viewed from the
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`perspective of a hypothetical artisan of ordinary skill in the relevant field at the
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`time of the invention. I understand that this skilled artisan is presumed to be aware
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`of the pertinent art in the field and has an ordinary level of creativity and
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`understanding.
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`27.
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`I understand from counsel that in prior Inter Partes Reviews (“IPR”)
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`of certain of the Challenged Patents, the Board adopted a definition of the person
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`of ordinary skill1 as follows:
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`[A] person of ordinary skill in the art at the time of the
`invention would have had a B.S. or M.S. in biochemistry,
`polymer chemistry, medicinal chemistry, pharmaceutical
`chemistry, or a related field with several years of practical
`experience. Alternatively…, the ordinary artisan would
`have had less practical experience but a Ph.D. in one of
`those fields, or an M.D. in dermatology, plastic surgery, or
`a specialty related to the clinical use of dermal fillers.
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`1 Throughout my declaration, I use the terms “skilled artisan” and “POSA” to refer
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`to the “person of ordinary skill in the art.”
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`In my opinion, related fields include organic chemistry, molecular biology,
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`materials science and engineering, chemical engineering, biomedical engineering,
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`biomolecular engineering, and bioengineering. (See Ex. 2100 at 255:2-19.)
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`28.
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`In my opinion, there is no reason to depart from the definition of the
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`person of ordinary skill (“POSA”) that was used in the earlier IPR proceedings
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`involving certain of the Challenged Patents, and I would adopt it again in the
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`current Inter Partes Reviews. I do not agree with Dr. DeVore’s proposed
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`definition of the POSA, which incorporates specialized skills and knowledge,
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`including those of other “team members” and those acquired by Dr. DeVore in his
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`various corporate executive roles, related to commercial aspects of the dermal filler
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`industry that even Dr. DeVore agrees the “ordinary skilled artisan” would not have
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`had. (See Ex. 2100 at 134:18-135:9.) In my opinion, the ordinary skilled artisan
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`attempting the development of a new HA dermal filler would have the training of a
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`scientist or physician, not of a regulatory liaison or sales or competitive
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`intelligence executive.
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`29.
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`In my opinion, ordinary skilled artisans who worked as corporate
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`executives could also have regulatory responsibilities, but such regulatory
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`responsibilities were in addition to, and not a part of, their scientific
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`responsibilities, and such regulatory responsibilities are not required to have the
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`level of ordinary skill in the art. An ordinary skilled scientist in this field would
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`not have routinely reviewed FDA filings, such as Summary of Safety and
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`Effectiveness Data (SSED) submissions or draft documentation, as part of his or
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`her review of technical literature in the field. Such documents do not contain the
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`type of scientific information that a skilled artisan typically would have been
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`seeking from, for example, peer-reviewed journal articles, textbooks, or patent
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`publications.
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`30.
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`In my opinion, the Board’s definition from the prior IPRs remains
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`appropriate. I disagree with Dr. DeVore’s proposal that the skilled artisan would
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`have been aware of the process by which FDA reviews dermal filler products,
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`would have been aware of how FDA communicates the results of such reviews to
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`the public, and would have known that once FDA approves a dermal filler it posts
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`information about that filler on its webpage. (See also Ex. 1032 at 225 (“It is clear
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`that many physicians who use these products to enhance their patients’ appearance
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`do not understand the US Food and Drug Administration (FDA) approval process
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`for devices such as lasers and injectable dermal fillers.”).)
` TECHNICAL BACKGROUND: HA’S PROPERTIES AND THE
`COMPLEXITIES OF DESIGNING INJECTABLE DERMAL
`FILLERS
`31. One of the hallmarks of aging is the development of skin wrinkles,
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`accompanied by loss of volume and elasticity of the skin. (Ex. 1011 at 369.)
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`Dermal and soft tissue fillers are gel-like products designed to be injected
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`under/into wrinkles and depressions to lift and volumize the dermal tissue. (See,
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`e.g., Ex. 1045 at 35; Ex. 2049 at 63-64.)
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`32. The first generation of tissue fillers used bovine collagen, a structural
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`protein in connective tissue, but the duration of effect was lim