UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`AMNEAL PHARMACEUTICALS LLC and AMNEAL
`
`PHARMACEUTICALS OF NEW YORK, LLC,
`
`Petitioners,
`
`v.
`
`ALMIRALL, LLC
`Patent Owner
`
`Case: IPR2018-006082019-00207
`
`U.S. Patent No. 9,161,9269,517,219
`
`DECLARATION OF BOZENA B. MICHNIAK-KOHN, Ph.D., FAAPS,
`M.R.Pharm.S.
`
`AMN1002
`
`Almirall, LLC
`Exhibit 2004
`Page 1
`
`

`

`Inter Partes Review of U.S. Patent No. 9,161,9269,517,219
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`I, Bozena B. Michniak-Kohn, do hereby declare as follows:
`
`Overview
`1.
`I am over the age of 18 and otherwise competent to make this
`
`
`
`I.
`
`declaration. I have been retained as an expert on behalf of Amneal Pharmaceuticals
`
`LLC and Amneal Pharmaceuticals of New York, LLC (“Amneal”). I understand
`
`from counsel this declaration is being submitted together with a petition for Inter
`
`Partes Review (“IPR”) of claims 1-68 of U.S. Patent No. 9,161,9269,517,219 (“the
`
`’926219 patent”) (AMN1001).
`
`2.
`
`I am being compensated for my time in connection with this IPR at my
`
`standard legal consultant rate of $650/hr. I have no personal or financial interest in
`
`Amneal or in the outcome of this proceeding.
`
`3.
`
`In preparing this declaration, I have reviewed the ’926219 patent
`
`(AMN1001) and considered each of the documents cited therein, in light of the
`
`general knowledge in the art before November 20, 2012. I have also relied upon my
`
`experience in the relevant art and considered the viewpoint of a person of ordinary
`
`skill in the art (“POSA”; defined in § IV) before November 20, 2012.
`
`4.
`
`Claims 1-As set forth below, claims 1-4 and 6-7 of the ’926219 patent
`
`would have been obvious over the prior art. I understand from counsel that another
`
`expert on behalf of Amneal will address claims 5 and 8. Each of the claimed
`
`elementscompositional components were known in the art for use in topical
`
`3
`
`Almirall, LLC
`Exhibit 2004
`Page 2
`
`

`

`Inter Partes Review of U.S. Patent No. 9,161,9269,517,219
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`
`compositions. Specifically, each of the elements were known for use in dapsone
`
`
`
`compositions, many in the same amounts as claimed. Each element is performing
`
`the same function it is known for in the art, and the prior art teaches that
`
`modifications to these amounts were within the skill of the art and would result in
`
`predictable changes to the compositions.
`
`5.
`
`This declaration sets forth my opinion that a POSA would have had a
`
`reason to arrive at the subject matter recited in claims 1-4 and 6-7 of the ’926219
`
`patent, with a reasonable expectation of success, by combining either:
`
`(1)
`
`the disclosures of Garrett (AMN1004), Nadau-Fourcade (AMN1005),
`
`and a POSA’s knowledge of the prior state of the art, or
`
`(2)
`
`the disclosures of Garrett (AMN1004), Bonacucina (AMN1015), and
`
`a POSA’s knowledge of the prior state of the art, as discussed in this
`
`declaration below.
`
`II. My background and qualifications
`6. My qualifications and credentials are fully set forth in my curriculum
`
`vitae, attached as AMN1003. I am an expert in the field of topical pharmaceutical
`
`compositions and transdermal drug delivery systems. Over the past 37 years, I have
`
`accumulated significant experience designing and testing novel formulations for
`
`topical and transdermal drug delivery systems including creams, gels, emulsions,
`
`and micro- and nano-carrier systems.
`
`
`
`4
`
`Almirall, LLC
`Exhibit 2004
`Page 3
`
`

`

`Inter Partes Review of U.S. Patent No. 9,161,9269,517,219
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`
`
`7.
`
`I received a B.S. in Pharmacy from DeMontfort University, Leicester,
`
`
`
`England, in 1977. I received my Ph.D. in Pharmacology from DeMontfort
`
`University in 1980. I held Postdoctoral Fellowships at the University of Florida’s
`
`College of Pharmacy from 1981-1983, and at the University of Bradford’s
`
`Postgraduate School of Studies in Pharmacy from 1983-1986. I am a member of the
`
`Royal Pharmaceutical Society of Great Britain (license #73637.)
`
`8.
`
`I was an Assistant Professor in the Department of Basic Pharmaceutical
`
`Sciences-Pharmaceutics (tenure-track) at the University of South Carolina’s College
`
`of Pharmacy from 1987-1993, an Associate Professor from 1993-1998, and Full
`
`Professor with tenure from 1998-2000. From 2000-2005, I was an Associate
`
`Professor in the Department of Physiology and Pharmacology at the University of
`
`Medicine and Dentistry of New Jersey- NJ Medical School. Since 2005, I have been
`
`a tenured Professor in Pharmaceutics at Rutgers- The State University of New
`
`Jersey.
`
`9.
`
`Since 2000, I have acted as the Director of the Laboratory for Drug
`
`Delivery at the New Jersey Center for Biomaterials at Rutgers. In 2011, I founded
`
`the Center for Dermal Research at Rutgers and continue to act as its Director. I am
`
`currently a member of the Editorial Boards of several peer-reviewed journals
`
`including the Clinical Dermatology Research Journal (SciTechnol), Research and
`
`Reports in Transdermal Drug Discovery (Dove Medical Press, Ltd.), Journal of Drug
`
`
`
`5
`
`Almirall, LLC
`Exhibit 2004
`Page 4
`
`

`

`Inter Partes Review of U.S. Patent No. 9,161,9269,517,219
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`
`Research and Development (Sciforshen), and the Journal of Drug Discovery
`
`
`
`(Hindawi Publishing Company).
`
`10. Since 2007, I have been a member of the Steering Committee of the
`
`Dermatopharmaceutics Focus Group of
`
`the American Association of
`
`Pharmaceutical Scientists. I have been an invited member of the College of NIH
`
`CSR reviewers since 2010. I have been a member of the Faculty of the National
`
`Institute for Pharmaceutical Technology and Education since 2014. Since 2014, I
`
`have acted as the Academic Chair of the Transdermal section of the Non-Invasive
`
`Macromolecule Consortium Working Group of the Catalent Applied Drug Delivery
`
`Institute. I have also organized numerous industry events and conferences.
`
`11.
`
`I have published hundreds of peer-reviewed articles, book chapters, and
`
`abstracts related to the field of topical drug delivery and pharmaceutical
`
`compositions. I have also been invited to speak about the field of topical drug
`
`delivery and formulations at numerous industry conferences.
`
`12.
`
`In view of my experiences and expertise outlined above and provided
`
`in my CV, I am an expert in the field of topical pharmaceutical compositions and
`
`transdermal drug delivery. For this reason, I am qualified to provide an opinion as
`
`to what a person of ordinary skill in the art would have understood, known, or
`
`concluded as of November 20, 2012.
`
`
`
`6
`
`Almirall, LLC
`Exhibit 2004
`Page 5
`
`

`

`Inter Partes Review of U.S. Patent No. 9,161,9269,517,219
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`
`
`
`III. Basis for my opinion
`13.
`In formulating my opinion, I have considered all documents cited
`
`herein, including the following:
`
`
`
`Amneal
`Exhibit #
`1001
`
`1003
`
`1004
`
`1005
`
`1007
`1008
`
`1009
`
`1010
`
`1011
`
`1012
`
`1013
`
`1014
`
`
`
`Description
`
`U.S. Patent No. 9,161,9269,517,219
`Curriculum Vitae for Bozena B. Michniak-Kohn, Ph.D., FAAPS,
`M.R.Pharm.S.
`International Patent Application Publication No. WO
`2009/061298
`(“Garrett”)
`International Application Publication No. WO 2010/072958
`(“Nadau-Fourcade”)
`U.S. Patent Publication No. 2006/0204526 (“Lathrop”)
`U.S. Patent Publication No. 2010/0029781 (“Morris”)
`Osborne, D.W., “Diethylene glycol monoethyl ether: an
`emerging solvent in topical dermatology products,” J.
`Cosmetic Derm.
`10:324-329 (2011) (“Osborne I”)
`Aczone® Gel 5% Product Label, approved July 7, 2005
`("Aczone®Physician’s Desk Reference, 65th ed., pp. 599-602
`(2011)
`(ACZONE Gel 5% Label")
`U.S. Patent No. 7,820,186 (“Orsoni”)
`Epiduo Product Label, approved December 8, 2008 (“Epiduo
`Label”)
`U.S. Patent Publication No. 2007/0190019 (“Guo”)
`Rowe, R.C. et al. (Eds.), Handbook of Pharmaceutical
`Excipients,
`
`6th Ed., Pharmaceutical Press: London, UK (2009)
`
`7
`
`Almirall, LLC
`Exhibit 2004
`Page 6
`
`

`

`Inter Partes Review of U.S. Patent No. 9,161,9269,517,219
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`
`
`
`
`
`
`
`
`
`
`
`
`Amneal
`Exhibit #
`
`1015
`
`1016
`1017
`1020
`
`1021
`
`1026
`
`1028
`
`1029
`
`1030
`
`1032
`
`
`14.
`
`Description
`
`Bonacucina, G. et al., “Characterization and Stability of
`Emulsion Gels Based on Acrylamide/Sodium
`Acryloyldimethyl Taurate Copolymer,” AAPS
`PharmaSciTech 10:368-375 (2009)
`(“Bonacucina”)
`U.S. Patent No. 5,863,560 (“Osborne II”)
`U.S. Patent No. 9,161,9269,517,219 File History
`ViscosityAffidavit of Carbopol® Polymers in Aqueous Systems,
`published August 13, 2010 (“Lubrizol Technical Data
`Sheet”)Christopher Butler
`Formulating Semisolid Products, published October 29, 2008
`(“Lubrizol Pharmaceutical Bulletin 21”)
`Sepineo™ P 600 Brochure
`Remington: The Science and Practice of Pharmacy, 21st
`Ed., Lippincott Williams & Wilkins: Baltimore, MD
`(2005)
`(“Remington”)
`Kim, J-Y et al., “Rheological properties and
`microstructures of Carbopol gel network system,” Colloid.
`Polym. Sci. 281:614–
`623(2003) (“Kim”)
`Neutralizing Carbopol® and Pemulen® Polymers in Aqueous
`and Hydro alcoholic Systems, published January 2002
`(“Noveon Technical Data Sheet”)
`Piskin, S. et al. “A review of the use of adapalene for the
`treatment
`of acne vulgaris,” Therapeutics and Clinical Risk Management
`3(4): 621–624 (2007) (“Piskin”)
`
`I understand from counsel that an obviousness analysis involves
`
`comparing a claim to the prior art to determine whether the claimed invention would
`
`
`
`8
`
`Almirall, LLC
`Exhibit 2004
`Page 7
`
`

`

`Inter Partes Review of U.S. Patent No. 9,161,9269,517,219
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`
`have been obvious to a person of ordinary skill in the art in view of the prior art, and
`
`
`
`in light of the general knowledge in the art. I also understand from counsel that when
`
`a POSA would have reached the claimed invention through routine experimentation,
`
`the invention may be deemed obvious. I understand from counsel that a finding of
`
`obviousness for a specific range or ratio in a patent can be overcome if the claimed
`
`range or ratio is proven to be critical to the performance or use of the claimed
`
`invention.
`
`15.
`
`I also understand from counsel that obviousness can be established by
`
`combining or modifying the teachings of the prior art to achieve the claimed
`
`invention. It is also my understanding from counsel that where there is a reason to
`
`modify or combine the prior art to achieve the claimed invention, there must also be
`
`a reasonable expectation of success in so doing. I understand from counsel that the
`
`reason to combine prior art references can come from a variety of sources, not just
`
`the prior art itself or the specific problem the patentee was trying to solve. And I
`
`understand from counsel that the references themselves need not provide a specific
`
`hint or suggestion of the alteration needed to arrive at the claimed invention; the
`
`analysis may include recourse to logic, judgment, and common sense available to a
`
`person of ordinary skill that does not necessarily require explication in any reference.
`
`I understand from counsel further that when considering the obviousness of an
`
`invention, one should also consider whether there are any secondary considerations
`
`
`
`9
`
`Almirall, LLC
`Exhibit 2004
`Page 8
`
`

`

`Inter Partes Review of U.S. Patent No. 9,161,9269,517,219
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`
`that support the nonobviousness of the invention.
`
`
`
`IV. Person of ordinary skill in the art
`16. Counsel has informed me that the critical date for assessing
`
`patentability of the ’926219 patent is November 20, 2012. Counsel also informed
`
`me that a person of ordinary skill in the art (“POSA”) is a hypothetical person in
`
`November 2012 presumed to be aware of all pertinent art, who thinks along
`
`conventional wisdom in the art, and is a person of ordinary creativity.
`
`17.
`
`In my opinion, a POSA would work as part of a multi-disciplinary team
`
`and have access to and draw upon individuals with comparable levels of education
`
`and experience in relevant disciplines that lie outside his or her primary training. In
`
`particular, the relevant POSA for the ’926219 patent would have the knowledge of
`
`both a clinician and a formulator of topical pharmaceutical compositions. I
`
`understand from counsel that another expert on behalf of Amneal will speak on those
`
`clinical aspects.
`
`18. For the formulator portion of a POSA, it is reasonable to think of a
`
`hypothetical POSA in 2012 as possessing a doctoral degree in pharmaceutics,
`
`chemistry or a related disciple such as pharmacology, or chemical engineering who
`
`also has practical experience (at least two years) of formulating topical drug delivery
`
`products, or someone possessing a Bachelors or Masters degree in one of the
`
`preceding disciplines but with a correspondingly greater level (at least four years) of
`
`
`
`10
`
`Almirall, LLC
`Exhibit 2004
`Page 9
`
`

`

`Inter Partes Review of U.S. Patent No. 9,161,9269,517,219
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`
`formulating topical drug delivery products. That is, the person of ordinary skill
`
`
`
`would have knowledge and skill relating to the use, function, and formulation of
`
`pharmaceutical actives and excipients; knowledge and training regarding the
`
`equipment, processes and techniques used to analyze and test formulation materials;
`
`and an understanding of pharmacokinetic principles and how they relate to drug
`
`development and use.
`
`V.
`
`State of the art before November 20, 2012
`19. Before November 20, 2012, the state of the art included the teachings
`
`provided by the references discussed in this Declaration. Additionally, a POSA,
`
`based on then-existing literature, would also have had general knowledge of the
`
`development of topical pharmaceutical compositions, including dapsone topical
`
`compositions.
`
`20. Dapsone, a bis(4-aminophenyl)sulfone, was first synthesized in 1908.
`
`(AMN1004,10 .1004, 10.) Dapsone possesses “several beneficial medicinal
`
`activities” and has been used to treat leprosy, bacterial, protozonal, and plasmonic
`
`infections, and pneumocystis carinii. (AMN1007, [0002].) Dapsone was also known
`
`to be an anti- inflammatory agent and has been used to treat skin diseases
`
`characterized by the abnormal infiltration of neutrophils, such as Dermatisis
`
`herpetiformis, linear IgA dermatosis, pustular psoriasis, pyoderma gangrenosum,
`
`Sweet’s Syndrome, acne vulgaris, including inflammatory and non-inflammatory
`
`
`
`11
`
`Almirall, LLC
`Exhibit 2004
`Page 10
`
`

`

`Inter Partes Review of U.S. Patent No. 9,161,9269,517,219
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`
`acne, and rosacea. (AMN1007, [00020003]; AMN1004, 3:14-15.)
`
`
`
`21. Dapsone was originally administered orally, however, oral use of
`
`dapsone is associated with hemolysis and hemolytic anemia. (AMN1004, 2:12- 14.)
`
`Thus, topical dapsone compositions are needed which can deliver a drug to the
`
`pilosebaceous unit. (Id., 20:8-10.) Garrett teaches that topical dapsone formulations
`
`are advantageous because the hematologic effects associated with oral dapsone
`
`are minimized. (Id., 11:22-23.) Development of such topical compositions was
`
`known in the art. (AMN1004, generally; AMN1007, [0004]; AMN1008, generally.)
`
`Many of these compositions were aqueous-based compositions. (AMN1004,
`
`Abstract; AMN1008, generally, AMN1016, generally.) In 2005, the U.S. Food and
`
`Drug Administration (“FDA”) granted marketing approval for Aczone® 5% for the
`
`treatment of acne vulgaris, which was an aqueous topical gel composition containing
`
`5% w/w dapsone. (AMN1010, 1 and 3.)
`
`22. Many of the topical dapsone compositions known in the art before 2012
`
`shared similar properties. Optimal compositions are those that contain both a
`
`dissolved portion of dapsone that crosses the stratum corneum of the skin and then
`
`passes into the epidermis/upper dermis to become systemically available, and an
`
`undissolved portion of dapsone that is retained in the stratum corneum to serve as a
`
`reservoir or to act in the supracorneum zone to reduce levels of Propionibacterium
`
`acnes. (AMN1004, 12:8-11; AMN1009, 4; AMN1016, 3:34- 38.) In the 5% dapsone
`
`
`
`12
`
`Almirall, LLC
`Exhibit 2004
`Page 11
`
`

`

`Inter Partes Review of U.S. Patent No. 9,161,9269,517,219
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`
`gel, “approximately one-third of the dapsone is dissolved and two-thirds of the
`
`
`
`dapsone is suspended as uniformly dispersed drug particulates.” (AMN1009, 4.)
`
`23. An important aspect of the known dapsone compositions is a
`
`solubilizing agent. Dapsone is insoluble in water and oils, and is soluble in ethanol,
`
`methanol, and acetone. (AMN1007, [0005].) For this reason, topical dapsone
`
`compositions in water or oils were difficult to develop. (Id.) Solubilizing agents for
`
`dapsone include organic solvents that are moderately soluble to miscible with water,
`
`which are capable of partially or fully dissolving dapsone either alone or in
`
`combination with water. (AMN1007, [0048]-[0049].) One preferred solubilizing
`
`agent for dapsone is ethoxydiglycol (i.e., diethylene glycol monoethyl ether).
`
`(AMN1007, [0055]-[0057]; AMN1004, 1314:13-14; AMN1010, 1; AMN1009, 3.)
`
`24. Ethoxydiglycol is used in hundreds of cosmetic products, as well as the
`
`FDA-approved 5% dapsone topical gel. (AMN1009, Abstract; AMN1010,
`
`generally.3.) Garrett discloses that ethoxydiglycol is a preferred solvent for use in
`
`dapsone topical compositions. (AMN1004, 1617:1-2.) Lathrop and Garrett
`
`specifically disclose topical dapsone compositions with 10-30% ethoxydiglycol.
`
`(AMN1004, 34:3; AMN1007, claim 26.) The 5% dapsone topical gel contains 25%
`
`ethoxydiglycol. (AMN1009, 2)
`
`25. Dapsone has a solubility profile in ethoxydiglycol/water mixtures that
`
`is favorable for formulating topical compositions. (AMN1009, 3, Figure 1.) Osborne
`
`
`
`13
`
`Almirall, LLC
`Exhibit 2004
`Page 12
`
`

`

`Inter Partes Review of U.S. Patent No. 9,161,9269,517,219
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`
`I discloses dapsone solubility as a function of increasing percentage of
`
`
`
`ethoxydiglycol mixed with water:
`
`
`
`
`
`(AMN1009, 3, Figure 1). A POSA would understand from Figure 1 that the
`
`amount of dissolved dapsone dissolved increases as the amount of
`
`ethoxydiglycol increases, and that the rate of dapsone dissolution increases as
`
`the ethoxydiglycol:water ratio increases above 20:80.
`
`26. Another important aspect of dapsone topical compositions is a
`
`
`
`14
`
`Almirall, LLC
`Exhibit 2004
`Page 13
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`

`

`Inter Partes Review of U.S. Patent No. 9,161,9269,517,219
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`
`polymeric thickening agent.1 1 A POSA would understand that the rheological
`
`
`
`properties of a topical composition must be maintained to ensure a suitable shelf
`
`life of the product. (AMN1011, 3:7-12.) These rheological properties define “the
`
`behavior and texture of the composition during application, but also the active
`
`principle’s release properties [] and the homogeneity of the product when the active
`
`principles are present therein in dispersed form. (Id., 3:12-16.) Morris teaches that
`
`“[t]he rate of absorption of dapsone from the solid microparticulate state can be
`
`controlled, at least in part, by the specifics of the microparticulate form of the solid
`
`material, e.g., the size, size distribution, shape, surface/volume ratio, polymorphic
`
`crystalline form, and hydration or solvation of the dapsone microparticles. For
`
`example, as is well known in the art, larger particles tend to dissolve or disperse
`
`more slowly due to lower surface area/volume ratio in comparison with smaller but
`
`similarly shaped particulates.” (AMN1008, [0004].) Thus, a POSA would
`
`understand that the polymeric thickening agent played an important role in the
`
`rheological properties and homogeneity of topical dapsone compositions.
`
`27. Prior art dapsone compositions contained hydrophilic and
`
`
`1 The terms “polymeric thickening agent,” “gelling agent,” and “viscosity
`builder” are used interchangeably throughout this Declaration.
`1 The terms “polymeric thickening agent,” “gelling agent,” and “viscosity
`builder” are used interchangeably throughout this Declaration.
`
`
`
`15
`
`Almirall, LLC
`Exhibit 2004
`Page 14
`
`

`

`Inter Partes Review of U.S. Patent No. 9,161,9269,517,219
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`
`hydroalcoholic thickening agents such as cross-linked acrylic acid polymers,
`
`
`
`commercially known as Carbopol®. (AMN1004, 13:17-18.) Other hydrophilic-
`
`phase thickening agents were also known to be suitable for dapsone, including
`
`acrylamide/sodium acryloyldimethyl taurate copolymer, such as Sepineo P 600®
`
`or Simulgel 600®. (AMN1005, 47:13-30-50:32 and 11:5-7; AMN1013, [0200].)
`
`Acrylamide/sodium acryloyldimethyltaurate copolymer in particular was approved
`
`by the FDA in 2008 in the Epiduo® product (adapalene/benzoyl peroxide topical
`
`gel.) (AMN1012, 6.)
`
`28. Bonacucina provides an extensive evaluation of Sepineo P 600 gels.
`
`According to Bonacucina, Sepineo P 600 “has self-gelling and thickening properties
`
`and the ability to emulsify oily phases, which make it easy to use in the formulation
`
`of gels and o/w emulsion gels.” (AMN1015, Abstract.) Gels prepared with 3% to 5%
`
`w/w Sepineo P 600 are characterized by “weak polymer-polymer interactions, an
`
`advantageous characteristic for topical administration, as the sample is thus easier to
`
`rub into the skin.” (Id.) Thus, a POSA would understand that acrylamide/sodium
`
`acryloyldimethyltaurate copolymer is a thickening agent useful for topical gel
`
`compositions, including dapsone topical compositions. Indeed, Bonacucina states that
`
`“Sepineo P 6oo600 is a prime candidate for use in the formulation of gels and
`
`emulsion gels with rheological properties suitable for topical administration.”
`
`(AMN1015, 7.) And it was generally known by 2012, for example from the SEPPIC
`
`
`
`16
`
`Almirall, LLC
`Exhibit 2004
`Page 15
`
`

`

`Inter Partes Review of U.S. Patent No. 9,161,9269,517,219
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`
`product brochure,2 that Sepineo P 600 was known in 2012 to be generally compatible
`
`
`
`with a variety of conditions: the product brochure for a commercially available
`
`acrylamide/sodium acryloyldimethyl taurate copolymer states that it isit was known
`
`to be compatible with a wide variety of solvents, including water, ethanol, acetone,
`
`glycerin, glycols, polar and non-polar oils, vegetable oils, silicone oils, and esters;
`
`
`2 4.
`In my experience, companies that manufacturer pharmaceutical
`excipients typically create and publish product brochures that companies use to
`market their excipients, provide information about the product, and describe the
`product’s features, functions, abilities, and/or capacities. In my experience, these
`companies typically include a date on each edition of a given brochure, so that
`purchasers and the general public can review the latest information available for a
`given product. These brochures are typically published on or around the revision
`date whereby the brochures are made available on manufacturer’s websites,
`distributed by sales staff, including them with samples and purchases, or publishing
`them to the public in trade journals. AMN 1026 mirrors the standard leaflet setup for
`pharmaceutical excipient manufacturers’ product brochures. Although I do not
`specifically recall the Sepineo P 600 brochure, the context and content of this
`document is consistent with my experience with product brochures: AMN1026 (1)
`identifies Sepineo P 600 as “belong[ing] to the SEPINEO™ new range [sic]
`specifically dedicated to your topical drug developments,” (2) provides technical
`details of the product (such as Sepineo™ P 600’s “benefits,” “thickening power,”
`“Emulsifying power,” and “formulation advice[].”), and (3) includes a date of “April
`2008” in the lower right corner of the second page. AMN1026, 1-2. Such
`information is often conveyed by excipient manufacturers in the ordinary course of
`advertising their products, and the information—including the date stated on the
`pamphlet—is a reliable indicator of the information contained within.
`I am familiar with Sepineo™ P 600, and the information contained in
`AMN1026 is consistent with the common knowledge, i.e., a POSA’s knowledge, of
`that product prior to the invention date. The fact that AMN1026 reflects the same
`information as a POSA would expect—i.e., the product name, technical information,
`and revision date—a POSA would find reliable the information contained on each
`point.
`
`
`
`17
`
`Almirall, LLC
`Exhibit 2004
`Page 16
`
`

`

`Inter Partes Review of U.S. Patent No. 9,161,9269,517,219
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`
`and can tolerate a wide pH and temperaturevariety of solvents, such as ethanol and
`
`
`
`propylene glycol, it thickens formulations over a large pH range., and it may be used
`
`in high shear mixing processes.3 (AMN1026.)1026, 4.)
`
`29. A final important aspect of the prior art dapsone compositions is a
`
`preservative. Preservatives are commonly used in topical compositions to maintain
`
`the potency, integrity, and safety of the compositions. (AMN1028, 20.) Garrett
`
`teaches using preservatives, such as methyl paraben, to prevent or diminish
`
`microorganism growth. (AMN1004, 13:29-30.) The working example disclosed in
`
`Garrett also contains methyl paraben, and Lathrop also discloses the use of methyl
`
`paraben as a preservative in topical dapsone compositions. (AMN1004, 24:30;
`
`AMN1007, [0082].) Mostly importantly, the prior art Aczone 5% commercial
`
`product contained methyl paraben. (AMN1010, 1.4.)
`
`
`3 This pre-2012 knowledge about the general compatibility of Sepineo P 600
`is further shown and corroborated by the December 2007 edition of Pharma &
`Healthcare News published by Alsiano. (AMN1034.) The face of AMN1034 states
`that Pharma & Healthcare News is a periodical that “is published twice a year and
`distributed to customers and other interested parties.” Id., 1. It states that 650 copies
`of this edition were circulated. Id. It further states that “SEPINEO™ P 600
`
`is able to thicken formulations over a wide pH range (2 to 12) . . . . Its compatibility
`with solvents like ethanol, propylene glycol, etc. is an advantage that makes it
`possible to elaborate formulas containing actives with poor solubility (hydro-
`alcoholic gels including up to 60% ethanol) or water sensible actives (anhydrous
`formulations).” AMN1034, 4.
`
`
`
`18
`
`Almirall, LLC
`Exhibit 2004
`Page 17
`
`

`

`Inter Partes Review of U.S. Patent No. 9,161,9269,517,219
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`
`
`
`VI. The ’926219 patent and its claims
`30.
`I understand that the ’926219 patent issued on October 20, 2015, and
`
`that the face page of the ’926219 patent it states that the ’926219 patent is
`
`currentlywas assigned to Allergan, Inc. (“AllerganI understand that the ’219 patent
`
`is currently assigned to Almirall, LLC (“Almirall”).4
`
`31. The face page of the ’926219 patent cites several related U.S. patent
`
`applications including U.S. Application No. 14/082,955, filed on November 18,
`
`2013, which claims the benefit of U.S. Provisional Application Nos. 61/728,403,
`
`filed on November 20, 2012, and 61/770,768, filed on February 28, 2013. I
`
`understand that the ’926219 patent is related to those applications. The earliest filing
`
`date of any of those listed applications is November 20, 2012. I understand that,
`
`based on that date, the earliest possible date to which the ’926219 patent may claim
`
`priority is November 20, 2012. I have been asked to provide my analysis of the
`
`’926219 patent based on prior art and the knowledge in the art before November 20,
`
`2012.
`
`32.
`
`I have considered the disclosure and claims of the ’926219 patent in
`
`light of the general knowledge in the art as of the earliest possible priority date of
`
`the ’926219 patent, which I understand is November 20, 2012. The ’926219 patent
`
`
`4 Throughout this declaration, I will refer to both Allergan and Almirall as
`“Almirall.”
`
`
`
`19
`
`Almirall, LLC
`Exhibit 2004
`Page 18
`
`

`

`Inter Partes Review of U.S. Patent No. 9,161,9269,517,219
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`
`specification generally describes “[d]apsone and dapsone/adapalene compositions []
`
`
`
`useful for treating a variety of dermatological conditions.” (AMN1001, Abstract.)
`
`33.
`
`I understand from counsel that in an IPR patent claim terms are given
`
`their broadest reasonable interpretation as understood by a POSA, in view of the
`
`patentthepatent and its file history. 5 It is my opinion that a POSA reading the
`
`’926219 patent would have understood that all the terms of claims 1-4 and 6-7 should
`
`be given their ordinary and customary meaning.
`
`34.
`
`I understand that the ’926219 patent has two independent claims, claims
`
`1 and 5,6, and foursix dependent claims. I understand that a dependent claim
`
`contains all the limitations of the claim from which it depends.
`
`A.
`Independent claims 1 and 56
`35. Claims 1 and 56 recite:
`
`1.
`
`1. A method for treating a dermatological
`
`condition selected from the group consisting of acne
`
`vulgaris and rosacea comprising administering to a
`
`subject having the dermatological condition selected
`
`from the group consisting of acne vulgaris and rosacea a
`
`
`5 5 I further understand that there is a different claim construction standard
`which will be employed by the Board in future cases. Because I understand that this
`alternative construction standard likewise looks primarily to the intrinsic record, my
`interpretation of the claims would be the same under this alternative standard.
`
`
`
`20
`
`Almirall, LLC
`Exhibit 2004
`Page 19
`
`

`

`
`
`Inter Partes Review of U.S. Patent No. 9,161,9269,517,219
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`
`
`
`
`topical pharmaceutical composition comprising: about
`
`7.5% w/w dapsone; about 30% w/w to about 40% w/w
`
`diethylene glycol monoethyl ether; about 2% w/w to
`
`about 6% w/w of a polymeric viscosity builder consisting
`
`ofcomprising acrylamide/sodium acryloyldimethyl
`
`taurate copolymer; and water; wherein the topical
`
`pharmaceutical composition does not comprise
`
`adapalene.
`
`2.
`
`5. A6. A method for treating a dermatological
`
`condition selected from the group consisting of acne
`
`vulgaris and rosacea comprising administering to a
`
`subject having the dermatological condition selected
`
`from the group consisting of acne vulgaris and rosacea a
`
`topical pharmaceutical composition comprising: about
`
`7.5% w/w dapsone; about 30% w/w diethylene glycol
`
`monoethyl ether; about 4% w/w of a polymeric viscosity
`
`builder consisting ofcomprising acrylamide/sodium
`
`acryloyldimethyl taurate copolymer; and water; wherein
`
`the topical pharmaceutical composition does not
`
`comprise adapalene.
`
`21
`
`Almirall, LLC
`Exhibit 2004
`Page 20
`
`

`

`Inter Partes Review of U.S. Patent No. 9,161,9269,517,219
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`
`(AMN1001, 15:2040-16:53 and 14-21.23-36.)
`
`
`
`B. Dependent claims 2-68
`36. Claims 2-45 depend directly from claim 1 and thus, I understand,
`
`contain each and every limitation of claim 1. Dependent claim 6 dependsclaims 7
`
`and 8 depend directly from claim 56 and thus, I understand, contains each and every
`
`limitation of claim 5.6. Claim 2 further requires that the diethylene glyc