`
`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.
`
`ALLERGAN, INC.
`Patent Owner
`
`_____________________
`
`Case: IPR2018-00608
`
`U.S. Patent No. 9,161,926
`_____________________
`
`DECLARATION OF BOZENA B. MICHNIAK-KOHN, Ph.D., FAAPS,
`M.R.Pharm.S.
`
`
`AMN1002
`
`

`

`Inter Partes Review of U.S. Patent No. 9,161,926
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`TABLE OF CONTENTS
`
`
`
`I. 
`II. 
`III. 
`IV. 
`V. 
`VI. 
`
`2. 
`
`3. 
`
`Overview ....................................................................................................... 3 
`My background and qualifications ............................................................... 4 
`Basis for my opinion ..................................................................................... 7 
`Person of ordinary skill in the art ................................................................. 9 
`State of the art before November 20, 2012 ................................................ 11 
`The ’926 patent and its claims .................................................................... 17 
`A. 
`Independent claims 1 and 5 ................................................................. 19 
`B.  Dependent claims 2-6 .......................................................................... 20 
`VII.  Claims 1-6 would have been obvious over Garrett in view of Nadau-
`Fourcade ..................................................................................................... 20 
`A.  Garrett (AMN1004) ............................................................................. 21 
`B.  Nadau-Fourcade (AMN1005) ............................................................. 23 
`C. 
`Independent claims 1 and 5 ................................................................. 23 
`1. 
`A POSA would have had reason to prepare a topical
`composition comprising “about 7.5% w/w dapsone,”
`“about 30% w/w to about 40% w/w diethylene glycol
`monoethyl ether,” and “water,” wherein “the
`composition does not comprise adapalene” ............................. 28 
`A POSA would have had a reason to prepare a topical
`composition comprising “about 2% w/w to about 6%
`w/w of a polymeric viscosity builder consisting of
`acrylamide/sodium
`acryloyldimethyl
`taurate
`copolymer” ............................................................................... 32 
`A POSA would have had reason to prepare a topical
`composition comprising “about 30% w/w diethylene
`glycol monoethyl ether” and “about 4% w/w of a
`polymeric
`viscosity
`builder
`consisting
`of
`acrylamide/sodium
`acryloyldimethyl
`taurate
`copolymer” ............................................................................... 34 
`The claimed components are well-known for use in
`topical compositions and therefore a POSA would
`have had a reasonable expectation of successfully
`combining them ........................................................................ 36 
`D.  Dependent Claims 2-4 and 6 ............................................................... 38 
`1
`
`4. 
`
`
`
`

`

`Inter Partes Review of U.S. Patent No. 9,161,926
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`
`
`2. 
`
`3. 
`
`4. 
`
`(a)  Claim 2 ........................................................................... 38 
`(b)  Claim 3 ........................................................................... 38 
`(c)  Claims 4 and 6 ............................................................... 39 
`VIII.  Claims 1-6 would have been obvious over Garrett in view of
`Bonacucina ................................................................................................. 40 
`A.  Bonacucina (AMN1015) ..................................................................... 40 
`B. 
`Independent claims 1 and 5 ................................................................. 42 
`1. 
`A POSA would have had reason to prepare a topical
`composition comprising “about 7.5% w/w dapsone,”
`“about 30% w/w to about 40% w/w diethylene glycol
`monoethyl ether,” and “water,” wherein “the
`composition does not comprise adapalene” ............................. 46 
`A POSA would have had reason to prepare a topical
`composition comprising “about 2% w/w to about 6%
`w/w of a polymeric viscosity builder consisting of
`acrylamide/sodium
`acryloyldimethyl
`taurate
`copolymer” ............................................................................... 50 
`A POSA would have had reason to prepare a topical
`composition comprising “about 30% w/w diethylene
`glycol monoethyl ether” and “about 4% w/w of a
`polymeric
`viscosity
`builder
`consisting
`of
`acrylamide/sodium
`acryloyldimethyl
`taurate
`copolymer” ............................................................................... 55 
`The claimed components are well-known for use in
`topical compositions and therefore a POSA would
`have had a reasonable expectation of successfully
`combining them ........................................................................ 56 
`C.  Dependent Claims 2-4 and 6 ............................................................... 58 
`1. 
`Claim 2 ..................................................................................... 59 
`2. 
`Claim 3 ..................................................................................... 59 
`3. 
`Claims 4 and 6 .......................................................................... 59 
`No objective indicia of non-obviousness exist ........................................... 60 
`A.  Allergan’s “unexpected” incompatibility and smaller particle
`size ....................................................................................................... 61 
`B.  There was no “teaching away” from combining the claimed
`components in the prior art .................................................................. 66 
`Conclusion .................................................................................................. 66 
`
`IX. 
`
`X. 
`
`
`
`2
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`

`

`Inter Partes Review of U.S. Patent No. 9,161,926
`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:
`I.
`
`Overview
`1.
`
`I am over the age of 18 and otherwise competent to make this
`
`declaration. I have been retained as an expert on behalf of Amneal
`
`Pharmaceuticals LLC and Amneal Pharmaceuticals of New York, LLC
`
`(“Amneal”). I understand this declaration is being submitted together with a
`
`petition for Inter Partes Review (“IPR”) of claims 1-6 of U.S. Patent No.
`
`9,161,926 (“the ’926 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 ’926 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 1-6 of the ’926 patent would have been obvious over the prior
`
`art. Each of the claimed elements were known in the art for use in topical
`
`compositions. Specifically, each of the elements were known for use in dapsone
`
`compositions, many in the same amounts as claimed. Each element is performing
`3
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`

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`
`
`Inter Partes Review of U.S. Patent No. 9,161,926
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`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 1-6 of the ’926 patent, with
`
`a reasonable expectation of success, by combining either:
`
`the disclosures of Garrett (AMN1004), Nadau-Fourcade (AMN1005), and a
`POSA’s knowledge of the prior state of the art, or
`
`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.
`
`7.
`
`I received a B.S. in Pharmacy from DeMontfort University, Leicester,
`
`England, in 1977. I received my Ph.D. in Pharmacology from DeMontfort
`
`
`
`4
`
`

`

`Inter Partes Review of U.S. Patent No. 9,161,926
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`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 Research and Development (Sciforshen), and the Journal of Drug Discovery
`
`(Hindawi Publishing Company).
`
`5
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`

`

`Inter Partes Review of U.S. Patent No. 9,161,926
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`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
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`

`

`Inter Partes Review of U.S. Patent No. 9,161,926
`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
`
`1015
`
`1016
`
`Description
`
`U.S. Patent No. 9,161,926
`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®
`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)
`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”)
`
`
`
`7
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`

`

`Inter Partes Review of U.S. Patent No. 9,161,926
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`Amneal
`Exhibit #
`1017
`
`1020
`
`1021
`
`1026
`
`1028
`
`1029
`
`1030
`
`1032
`
`
`
`Description
`
`U.S. Patent No. 9,161,926 File History
`Viscosity of Carbopol® Polymers in Aqueous Systems, published
`August 13, 2010 (“Lubrizol Technical Data Sheet”)
` 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”)
`
`14.
`
`I understand that an obviousness analysis involves comparing a claim
`
`to the prior art to determine whether the claimed invention would 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 that when a POSA would
`
`have reached the claimed invention through routine experimentation, the invention
`
`may be deemed obvious. I understand that a finding of obviousness for a specific
`
`8
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`

`
`
`Inter Partes Review of U.S. Patent No. 9,161,926
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`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 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 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 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 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 further that when
`
`considering the obviousness of an invention, one should also consider whether
`
`there are any secondary considerations 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 ’926 patent is November 20, 2012. Counsel also informed me
`
`that a person of ordinary skill in the art (“POSA”) is a hypothetical person in
`
`
`
`9
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`

`

`Inter Partes Review of U.S. Patent No. 9,161,926
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`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 ’926 patent would have the
`
`knowledge of both a clinician and a formulator of topical pharmaceutical
`
`compositions. I understand 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 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
`
`10
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`

`

`Inter Partes Review of U.S. Patent No. 9,161,926
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`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 .) 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 acne, and rosacea.
`
`(AMN1007,[0002]; 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
`
`
`
`11
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`

`

`Inter Partes Review of U.S. Patent No. 9,161,926
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`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 gel, “approximately one-third of the dapsone is dissolved
`
`and two-thirds of the dapsone is suspended as uniformly dispersed drug
`
`particulates.” (AMN1009, 4.)
`
`12
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`Inter Partes Review of U.S. Patent No. 9,161,926
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`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, 13:13-14; 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.) Garrett discloses that ethoxydiglycol is a preferred solvent for use in
`
`dapsone
`
`topical compositions. (AMN1004, 16:1-2.) Lathrop and Garrett
`
`specifically disclose topical dapsone compositions with 10-30% ethoxydiglycol.
`
`(AMN1004, 3:3; 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.)
`
`13
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`Inter Partes Review of U.S. Patent No. 9,161,926
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`Osborne 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.
`
`
`
`14
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`Inter Partes Review of U.S. Patent No. 9,161,926
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`26. Another important aspect of dapsone topical compositions is a
`
`
`
`polymeric thickening agent.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.
`
`
`1 The terms “polymeric thickening agent,” “gelling agent,” and “viscosity
`builder” are used interchangeably throughout this Declaration.
`
`
`
`15
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`

`

`Inter Partes Review of U.S. Patent No. 9,161,926
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`27. Prior art dapsone compositions contained hydrophilic and
`
`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, 47:13-30-32 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 6oo is a prime candidate for use in the
`
`formulation of gels and emulsion gels with rheological properties suitable for
`16
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`
`
`Inter Partes Review of U.S. Patent No. 9,161,926
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`topical administration.” (AMN1015, 7.) And Sepineo 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 is compatible with a wide variety of solvents, including water,
`
`ethanol, acetone, glycerin, glycols, polar and non-polar oils, vegetable oils,
`
`silicone oils, and esters; and can tolerate a wide pH and temperature range.
`
`(AMN1026.)
`
`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.)
`
`VI. The ’926 patent and its claims
`30.
`I understand that the ’926 patent issued on October 20, 2015, and that
`
`the face page of the ’926 patent it states that the ’926 patent is currently assigned
`
`to Allergan, Inc. (“Allergan”).
`
`
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`17
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`

`

`Inter Partes Review of U.S. Patent No. 9,161,926
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`31. The face page of the ’926 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 ’926 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 ’926 patent may claim
`
`priority is November 20, 2012. I have been asked to provide my analysis of the
`
`’926 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 ’926 patent in light
`
`of the general knowledge in the art as of the earliest possible priority date of the
`
`’926 patent, which I understand is November 20, 2012. The ’926 patent
`
`specification generally describes “[d]apsone and dapsone/adapalene compositions
`
`[] useful for treating a variety of dermatological conditions.” (AMN1001,
`
`Abstract.)
`
`33.
`
`I understand that in an IPR patent claim terms are given their broadest
`
`reasonable interpretation as understood by a POSA, in view of the patent and its
`
`file history. It is my opinion that a POSA reading the ’926 patent would have
`
`18
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`

`

`Inter Partes Review of U.S. Patent No. 9,161,926
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`understood that all the terms of claims 1-6 should be given their ordinary and
`
`customary meaning.
`
`34.
`
`I understand that the ’926 patent has two independent claims, claims 1
`
`and 5, and four dependent claims. I understand that a dependent claim contains all
`
`the limitations of the claim from which it depends.
`
`A.
`Independent claims 1 and 5
`35. Claims 1 and 5 recite:
`
`1. A 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
`
`of acrylamide/sodium acryloyldimethyl taurate
`
`copolymer; and water; wherein the composition does not
`
`comprise adapalene.
`
`5. 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 of acrylamide/sodium
`
`acryloyldimethyl taurate copolymer; and water; wherein
`
`the composition does not comprise adapalene.
`19
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`

`Inter Partes Review of U.S. Patent No. 9,161,926
`Declaration of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S.
`(Exhibit 1002)
`
`
`(AMN1001, 15:20-16:5 and 14-21.)
`B. Dependent claims 2-6
`36. Claims 2-4 depend directly from claim 1 and thus, I understand,
`
`contain each and every limitation of claim 1. Dependent claim 6 depends directly
`
`from claim 5 and thus, I understand, contains each and every limitation of claim 5.
`
`Claim 2 further requires that the diethylene glycol monoethyl ether concentration
`
`is about 30% w/w. Claim 3 further requires that the polymeric viscosity builder
`
`concentration is about 4% w/w. Claims 4 and 6 further require methyl paraben.
`
`(AMN1001, 16:6-13 and 22-23.)
`
`VII. Claims 1-6 would have been obvious over Garrett in view of Nadau-
`Fourcade
`37.
`
`I understand that Garrett (AMN1004) qualifies as prior art to the ’926
`
`patent claims because it published in 2009, which is prior to the filing date of the
`
`’926 patent. I also understand that Nadau-Fourcade (AMN1005) qualifies as prior
`
`art to the ’926 patent claims because it published in 2010, which is prior to the
`
`filing date of the ’926 patent.
`
`38.
`
`In my opinion, claims 1-6 would have been obvious to a POSA as of
`
`at least November 20, 2012, over Garrett and Nadau-Fourcade. I reached