`
`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: IPR2018-00608
`
`U.S. Patent No. 9,161,926
`_____________________
`
`Second Declaration of Elaine S. Gilmore, M.D., Ph.D.
`
`
`AMN1034
`
`

`

`
`
`Inter Partes Review of U.S. Patent No. 9,161,926
`Second Declaration of Elaine S. Gilmore, M.D., Ph.D.
`(Exhibit 1034)
`
`TABLE OF CONTENTS
`
`I. 
`Overview .......................................................................................................... 1 
`Scope of testimony and documents considered ............................................... 1 
`II. 
`III.  The existence of other alternative acne treatments would not have lead a
`POSA away from dapsone. ........................................................................................ 3 
`A.  A POSA would not have ignored dapsone as an anti-acne
`treatment. ............................................................................................... 4 
`A POSA would not have ignored dapsone’s efficacy against
`rosacea. .................................................................................................. 8 
`It would have been obvious to a POSA to use dapsone as a monotherapy. .... 9 
`
`B. 
`
`IV. 
`
`
`i
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`

`

`Inter Partes Review of U.S. Patent No. 9,161,926
`Second Declaration of Elaine S. Gilmore, M.D., Ph.D.
`(Exhibit 1034)
`
`I, Elaine S. Gilmore, hereby declare as follows.
`
`I.
`
`Overview
`1.
`
`I am over the age of eighteen (18) and otherwise competent to make
`
`this declaration.
`
`2.
`
`I have been retained as an expert witness on behalf of Petitioners
`
`Amneal Pharmaceuticals LLC and Amneal Pharmaceuticals of New York, LLC
`
`for the above-captioned inter partes review (“IPR”). I am being compensated for
`
`my time in connection with this IPR at my standard consulting rate, which is
`
`$500/hr. I understand that the petition for IPR involves U.S. Patent No. 9,161,926
`
`(“the ’926 patent”), AMN1001, which resulted from U.S. Application No.
`
`14/082,955 (“the ’955 application”), filed on November 18, 2013, naming Kevin S.
`
`Warner, Ajay P. Parashar, Vijaya Swaminathan, and Varsha Bhatt as inventors.
`
`The ’926 patent issued on October 20, 2015, from the ’955 application.
`
`II.
`
`Scope of testimony and documents considered
`3.
`
`Previously, I submitted a declaration in support of Amneal’s Petition.
`
`See AMN1018. I understand from Counsel for Amneal that Almirall submitted in
`
`support of its Patent Owner’s Response (“POR”) the declaration of Julie Harper,
`
`MD. EX2022 (“Harper Decl.”). I have been asked to respond to the portions of Dr.
`
`Harper’s declaration relied upon by Patent Owner Almirall.
`
`4.
`
`In formulating my opinions, I considered the following documents:
`
`- 1 -
`
`

`

`Exhibit or
`Paper No.
`
`1001
`
`1004
`
`1007
`
`1008
`1010
`1012
`1018
`1022
`
`1023
`
`1024
`1025
`
`1027
`
`1035
`
`1036
`
`1037
`1038
`
`Inter Partes Review of U.S. Patent No. 9,161,926
`Second Declaration of Elaine S. Gilmore, M.D., Ph.D.
`(Exhibit 1034)
`
`Description
`Warner et al., “Topical Dapsone and Dapsone/Adaplene
`Compositions and Methods for Use Thereof, U.S. Patent No.
`9,161,926 (filed November 18, 2013; issued October 20, 2015)
`Garrett et al., “Topical Treatment With Dapsone in G6PD-
`Deficient Patients” WO 2009/061298 (filed November 7, 2007;
`published May 14, 2009)
`Lathrop, “Emulsive Composition Containing Dapsone” U.S.
`Pat. Appl. Publ. No. 2006/0204526 (filed February 13, 2006;
`published September 14, 2006)
`U.S. Patent Publication No. 2010/0029781 (“Morris”)
`ACZONETM Gel 5% Package Insert
`Epiduo Product Label, approved December 8, 2008 (“Epiduo
`Label”)
`Declaration of Elaine S. Gilmore, M.D., Ph.D.
`Wozel, D., “Innovative Use of Dapsone” Dermatol. Clin. 28:
`599–610 (2010)
`Thiboutot, D., et al., “Pharmacokinetics of Dapsone Gel, 5%
`for the Treatment of Acne Vulgaris” Clin. Pharmacokinet. 46:
`697-712 (2007)
`Nguyen, R. and Su, J., “Treatment of Acne Vulgaris” Pediatrics
`and Child Health 21: 119-125 (2010)
`Williams, H., et al., “Acne vulgaris” Lancet 379: 361–72 (2012)
`Barclay, L., “Use of Topical Corticosteroids for Dermatologic
`Conditions Reviewed” Medscape - Jan 21, 2009, accessed from
`https://www.medscape.com/viewarticle/587159_print
`Tanghetti, E., et al., “The Efficacy and Tolerability of Dapsone
`So/o Gel in Female vs Male Patients With Facial Acne Vulgaris:
`Gender as a Clinically Relevant Outcome Variable,” Journal of
`Drugs in Dermatology 11: 1417-1421 (2012)
`Fleisher, Jr., A., et al., “Dapsone Gel So/o in Combination With
`Adapalene Gel 0.1 o/o, Benzoyl Peroxide Gel 4 o/o or
`Moisturizer for the Treatment of Acne Vulgaris: A 12-Week,
`Randomized, Double-Blind Study,” Journal of Drugs In
`Dermatology 9: 33-40 (2010)
`Physicians’ Desk Reference, 60th ed., Solagé®, pp. 740-742
`(2006)
`Physicians’ Desk Reference, 61st ed., Tri-Luma® , pp. 1213-
`
`- 2 -
`
`

`

`Inter Partes Review of U.S. Patent No. 9,161,926
`Second Declaration of Elaine S. Gilmore, M.D., Ph.D.
`(Exhibit 1034)
`
`1215 (2007)
`Physicians’ Desk Reference, 63rd ed., Ziana® , pp. 1942-1945
`(2009)
`Physicians’ Desk Reference, 65th ed., Veltin®, pp. 3145-3148
`(2011)
`International Patent Application Publication No. WO
`2011/014627
`International Patent Application Publication No. WO
`2009/108147
`MaryAnn Steiner, Dapsone Topical Gel for Acne, J. Pharm. Soc.
`Wisc. 12(6): 67-71 (2009)
`Kirk A. James, Emerging drugs for acne, Expert. Opin.
`Emerging Drugs 14(4): 649-659 (2009)
`Barry Coutinho, Dapsone (Aczone) 5% Gel for the Treatment of
`Acne, American Family Physician (Dec. 2010)
`Declaration of Julie Harper, M.D.
`John Kraft & Anatoli Freiman, Management of acne, 183
`Canadian Med. Assoc. J. E430-E435 (2011)
`Stephen Titus & Joshua Hodge, Diagnosis and Treatment of
`Acne, 86 Am. Family Physician 734-740 (2012)
`Dina Anderson, Finding a Place for Topical Anti-inflammatory
`Acne Therapy, Practical Dermatology 17-18 (July 2009)
`(“Anderson”)
`Michael Ghods et al., The Role of Dapsone Gel in the Acne
`Armamentarium, The Dermatologist (June 10, 2010)
`
`1039
`
`1040
`
`2005
`
`2006
`
`2013
`
`2016
`
`2017
`2022
`2024
`
`2026
`
`2040
`
`2041
`
`
`III. The existence of other alternative acne treatments would not have led a
`POSA away from dapsone.
`5.
`
`I understand that Almirall and Dr. Harper argue that a POSA would
`
`not have selected dapsone for two reasons: (1) that Almirall contends that benzoyl
`
`peroxide and retinoids were more common first-line acne treatments, and (2) that
`
`dapsone was ineffective against rosacea. I disagree for at least the reasons below.
`
`- 3 -
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`

`

`Inter Partes Review of U.S. Patent No. 9,161,926
`Second Declaration of Elaine S. Gilmore, M.D., Ph.D.
`(Exhibit 1034)
`A. A POSA would not have ignored dapsone as an anti-acne
`treatment.
`
`6.
`
`I understand from Counsel that Almirall contends that a POSA would
`
`not have selected dapsone as an acne treatment because other drugs—namely,
`
`retinoids and benzoyl peroxide—were more common first-line acne treatments. I
`
`disagree.
`
`7.
`
`As an initial matter, I understand that Almirall cited a portion of my
`
`deposition in which I testified that I did not use dapsone as a first-line treatment. In
`
`my opinion, that fact is irrelevant to the obviousness of selecting dapsone as an
`
`acne treatment. The simple fact of the matter is that before the ’926 patent,
`
`dermatologists (myself included) were prescribing topical dapsone for the
`
`treatment of acne vulgaris—as instructed by ACZONE Gel, 5% label. AMN1010,
`
`8-9. And as I explain below, I was not the only doctor who found dapsone to be
`
`useful; Almirall’s expert, Dr. Harper, actually published an article touting the
`
`benefits of using dapsone, particularly in females. AMN1035, Abstract, 1.
`
`8.
`
`Besides clinical practice, dapsone was also known to be effective as a
`
`monotherapy for the treatment of acne vulgaris. First, ACZONE Gel, 5% was
`
`approved by the U.S. Food and Drug Administration for the treatment of acne
`
`vulgaris. AMN1010, 3. Regardless of whether it was first-line or second-line, a
`
`POSA would have had a reason to select dapsone as an acne treatment based on its
`
`FDA-approved indication.
`
`- 4 -
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`

`

`Inter Partes Review of U.S. Patent No. 9,161,926
`Second Declaration of Elaine S. Gilmore, M.D., Ph.D.
`(Exhibit 1034)
`Second, besides the FDA-approved treatment indication, many other
`
`9.
`
`references taught that topical dapsone compositions were effective acne
`
`treatments—further confirming a POSA’s selection—including:
`
` AMN1008: “One topical formulation for the treatment of acne that
`
`has found wide acceptance is Aczone®, a topical formulation of the
`
`bioactive drug dapsone that is in the physical form of an aqueous gel
`
`containing dapsone both in solution and in the solid phase.”
`
`AMN1008, ¶[0004].
`
` EX2005: “The anti-acne molecule dapsone is marketed as a
`
`commercial product Aczone®. Aczone® is a 5% dapsone gel with a
`
`gritty texture due to insoluble particles of dapsone drugs. The
`
`insolubility of dapsone limits the bioavailability of dapsone upon
`
`application and its absorption through the skin and is therefore
`
`administered twice daily.” EX2005, 3:10-24.
`
` EX2013: “Dapsone-treated patients were more likely to have
`
`treatment success [versus vehicle] at 12 weeks (p<0.001).” EX2013,
`
`3-4.
`
` EX2016: “two recent studies have shown that a 5% dapsone topical
`
`gel solution is effective in reducing the amount of both non-
`
`inflammatory and inflammatory acne lesions when used as a
`
`- 5 -
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`

`

`Inter Partes Review of U.S. Patent No. 9,161,926
`Second Declaration of Elaine S. Gilmore, M.D., Ph.D.
`(Exhibit 1034)
`monotherapy and applied twice a day for 12 weeks. The most
`
`pronounced effect was in treating the inflammatory lesions, which
`
`decreased by 47.5% after 12 weeks of treatment”. EX2016, 5.
`
` EX2017: “Studies show that dapsone gel has modest effectiveness in
`
`the treatment of moderately severe inflammatory and
`
`noninflammatory acne.” EX2017, 1.
`
` EX2024: “A large multicentre randomized controlled trial in
`
`adolescents with acne found that when the gel was applied twice daily
`
`on the affected areas, 40% of the treatment group and 28% of the
`
`placebo group (p < 0.001) achieved the desired outcome at 12 weeks.
`
`The same trial, and an additional study, found that topical dapsone 5%
`
`gel is a safe treatment option in patients with a deficiency in glucose-
`
`6-phosphate dehydrogenase.” EX2024, 5.
`
` EX2040: “Several publications have presented and reviewed the
`
`efficacy of topical dapsone gel 5% in treating mild to moderately
`
`severe acne. In 12-week clinical trials comparing topical dapsone to
`
`vehicle, treated patients had greater improvements in investigator’s
`
`global acne assessment and mean percentage reduction in
`
`inflammatory, non-inflammatory, and total lesion counts, compared to
`
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`

`Inter Partes Review of U.S. Patent No. 9,161,926
`Second Declaration of Elaine S. Gilmore, M.D., Ph.D.
`(Exhibit 1034)
`controls. Statistically significant improvement in lesion counts was
`
`evident by week four.” EX2040, 1.
`
` EX2041: “Clinical trials have demonstrated reductions in acne lesions
`
`with 5% dapsone gel use, particularly for inflammatory lesions.”
`
`EX2041, 1-2.
`
`10.
`
`In addition to the prior art concerning topical dapsone’s efficacy,
`
`Garrett’s disclosure is clear: topically applied dapsone is useful for the treatment of
`
`acne. AMN1004, 3:9-15; 4:25-31. Garrett discusses the FDA-approved 5%
`
`formulation, which was “indicated for the topical treatment of acne vulgaris.”
`
`AMN1004, 10:4-12, 12:1-4; AMN1010, 3. Garrett explained that the existing 5%
`
`formulation was “developed to deliver therapeutic concentrations of dapsone to the
`
`skin.” AMN1004, 10:6-7. Garrett further discloses clinical study results which,
`
`while primarily directed to showing the safety of topical dapsone, also confirmed
`
`that dapsone was effective in treating inflammatory and non-inflammatory acne.
`
`See AMN1004, 28:10-29:5. For example, Garrett explains that “Eficacy [sic]
`
`variables collected in this study were lesion counts (inflammatory, non-
`
`inflammatory, and total). In all lesion categories, AczoneTM-treated subjects
`
`experienced larger absolute reductions in lesions than vehicle-treated subjects after
`
`12 weeks in the first treatment period.” Id., 28:10-29:2. Garrett further explained
`
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`

`

`Inter Partes Review of U.S. Patent No. 9,161,926
`Second Declaration of Elaine S. Gilmore, M.D., Ph.D.
`(Exhibit 1034)
`that “the absolute reduction in lesion counts was numerically better with AczoneTM
`
`treatment for all lesion categories.” Id., 29:24-25.
`
`11.
`
` Similarly, Lathrop taught that dapsone could be used to treat several
`
`skin conditions, including acne vulgaris. AMN1007, ¶[0003]. Like Garrett,
`
`Lathrop disclosed multiple concentrations of dapsone, including a 7.5%
`
`concentration described as “preferred,” that differed from the existing FDA-
`
`approved 5% formulation. AMN1007, ¶[0014]. Dr. Harper herself published on
`
`dapsone around the time of the ’926 patent—informing her colleagues that dapsone
`
`was an effective treatment for acne. AMN1035, 1. In December of 2012, just
`
`weeks after what I understand is the date of the alleged invention of the ’926
`
`patent, Dr. Harper published an article exclusively about dapsone. There, she
`
`explained that dapsone “is an effective topical treatment for patients with acne
`
`vulgaris.” Id. Notably, the reference she cites for this point was published in 2007,
`
`well before the alleged invention date. Id., 4, 8. In my opinion, Dr. Harper’s work
`
`confirms that a POSA would not have discarded or otherwise ignored dapsone as
`
`an acne treatment regardless of whether it was a first-line or a second-line
`
`treatment.
`
`B. A POSA would not have ignored dapsone’s efficacy against
`rosacea.
`12. Almirall and Dr. Harper’s contention that dapsone was not known to
`
`be effective for the treatment of rosacea is contrary to the published art at the time
`
`- 8 -
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`

`

`Inter Partes Review of U.S. Patent No. 9,161,926
`Second Declaration of Elaine S. Gilmore, M.D., Ph.D.
`(Exhibit 1034)
`of invention. Garrett is clear: dapsone treats “inflammatory acne, non-
`
`inflammatory acne or rosacea.” AMN1004, 3:13-15. Even Almirall’s art
`
`establishes that dapsone is useful for the treatment of rosacea. See EX2006,
`
`Abstract (“The methods described herein provide treatment of rosacea using
`
`topical formulations of dapsone.”); see also EX2005, 4:16-24 (the disclosed
`
`dapsone and adapalene formulation was useful “in the treatment of dermatological
`
`conditions such as … rosacea.”).
`
`IV.
`
`It would have been obvious to a POSA to use dapsone as a
`monotherapy.
`13.
`
` Dr. Harper testified that using a topical dapsone composition that
`
`excludes adapalene would not have been obvious. I disagree.
`
`14. Garrett contains an extensive discussion of topical compositions
`
`containing dapsone as the only active agent, and methods of using such
`
`compositions to treat skin conditions, such as inflammatory acne, non-
`
`inflammatory acne, and rosacea, among other skin conditions. AMN1004, 3:13-15;
`
`4:23-24. Garrett does not mention adapalene. Accordingly, a POSA viewing
`
`Garrett would have understood that topical compositions of dapsone, without any
`
`other active agents, were effective acne treatments. This would have been
`
`consistent with other prior art references: (1) the ACZONE Gel, 5% label is
`
`indicated to treat acne vulgaris and does not condition its efficacy on the use of
`
`other active agents (AMN1010, 3), (2) Morris’s teaching that topical dapsone, in
`
`- 9 -
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`

`

`Inter Partes Review of U.S. Patent No. 9,161,926
`Second Declaration of Elaine S. Gilmore, M.D., Ph.D.
`(Exhibit 1034)
`the form of Aczone® 5% gel, is effective for the treatment of acne (AMN1008,
`
`¶[0004]); (3) Steiner’s teaching that the studies it discussed showing topical
`
`dapsone’s efficacy against acne “only evaluated monotherapy” (EX2013, 3), and
`
`(4) James’ teaching that the studies it discussed “used [topical dapsone] as a
`
`monotherapy.” EX2016, 5.
`
`15. The opinions offered by Dr. Harper as to why a POSA would seek to
`
`make a single composition containing both dapsone and adapalene are flawed. Her
`
`primary logic is that, around 2012, there was an interest in developing combination
`
`products. EX2022, ¶¶164-166. Based on this desire to develop combination
`
`products, she opines that the second agent (alongside dapsone) “would have been
`
`adapalene.” Id., ¶167. She then goes on to discuss various reasons to combine
`
`adapalene with dapsone. Id., ¶¶168-172. I disagree that a POSA would have looked
`
`exclusively to combination treatments in 2012 for the treatment of acne, a POSA
`
`also would have considered individual drugs, both for use alone as a monotherapy
`
`and for administration with a second, separately formulated drug.
`
`16. Dr. Harper touts the alleged benefits of combination treatments: (1)
`
`improved compliance; and (2) ability to address multiple mechanisms of action of
`
`acne. Neither of these reasons would have compelled a POSA to stop treating acne
`
`with monotherapies or treatment regimens using multiple monotherapies; and
`
`neither purported benefit requires a combination product. EX2022, ¶166. For
`
`- 10 -
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`

`

`Inter Partes Review of U.S. Patent No. 9,161,926
`Second Declaration of Elaine S. Gilmore, M.D., Ph.D.
`(Exhibit 1034)
`example, I explained in my previous declaration that a patient suffering from acne
`
`is highly motivated to comply with whatever prescription he or she is given.
`
`AMN1018, ¶29. This is because the symptoms of acne (lesions) are visible, and
`
`patients are very cognizant that others can see their acne. Patients want to manage
`
`the condition because it helps improve their self-esteem. See id.; AMN1025, 1.
`
`Thus, a POSA would not have discarded monotherapy acne treatments or treatment
`
`regimens using multiple monotherapies because of compliance concerns. As for
`
`treating the multiple pathways of acne, a POSA could already accomplish that
`
`objective by co-administering multiple drugs to a single patient.
`
`17.
`
`In addition, combination products have drawbacks in terms of dosing
`
`frequency. When prescribing drugs to treat a patient, it is important to balance
`
`efficacy and tolerability. Frequently, topical acne treatments are tolerated
`
`differently by different patients, especially patients with sensitive skin.
`
`Administering separate drugs to a patient helps improve patient tolerability as a
`
`patient might be able to tolerate dapsone twice daily but might not be able to
`
`tolerate another acne treatment administered on the same treatment schedule.
`
`Keeping the topical acne treatments separate allows the POSA to customize a
`
`treatment regimen to a patient in a way that combination products do not allow.
`
`18. Even if a POSA had considered combination products, Dr. Harper is
`
`also incorrect that a POSA would have used adapalene to the exclusion of all other
`
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`

`

`Inter Partes Review of U.S. Patent No. 9,161,926
`Second Declaration of Elaine S. Gilmore, M.D., Ph.D.
`(Exhibit 1034)
`acne drugs. Dr. Harper provides no reason why a POSA (assuming they wanted to
`
`make a combination product with dapsone) would not have considered benzoyl
`
`peroxide—“the oldest and most widely used topical agent for the treatment of non-
`
`inflammatory and inflammatory acne vulgaris.” EX2016, 2. In fact, the Anderson
`
`reference cited by Dr. Harper confirms that a POSA would have considered
`
`benzoyl peroxide. See EX2040, 2 (if dapsone “is used in conjunction with other
`
`topical agents, … it may be wise to reduce the application of dapsone to once daily
`
`and substitute a retinoid or antimicrobial, such as benzoyl peroxide, at the other
`
`application time.”).
`
`19. Even if a POSA sought to limit their consideration to only topical
`
`retinoids, like adapalene, “[t]he most commonly available topical retinoids are
`
`tretinoin, adapalene, and tazarotene.” EX2024, 2. And while some evidence
`
`suggests that adapalene is the best tolerated retinoid, other evidence suggests that
`
`tazarotene is the most effective, “[t]here is no evidence that any formulation is
`
`superior to another.” EX2026, 2. That explains why Anderson identified retinoids
`
`as a class and not a specific drug among the three. See EX2040, 2. These drugs
`
`were, and still are, generally considered interchangeable; selection of one amongst
`
`them is a matter of personal preference. Thus, if a POSA sought to develop a
`
`combination product with dapsone, the POSA would not have limited their
`
`consideration to adapalene. Based on Dr. Harper’s pathways theory, a POSA
`
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`Inter Partes Review of U.S. Patent No. 9,161,926
`Second Declaration of Elaine S. Gilmore, M.D., Ph.D.
`(Exhibit 1034)
`would have also found it reasonable to co-prescribe azelaic acid with dapsone
`
`because azelaic acid was known to work on keratinization and p. acnes, while
`
`dapsone worked primarily on inflammation. See EX2022, ¶66 (citing AMN1025).
`
`20. The history of combination acne treatments also supports my view. In
`
`2012 and today, there is only one adapalene combination acne treatment, a
`
`combination of adapalene and benzoyl peroxide, sold under the tradenames
`
`Epiduo, Epiduo Forte, and in generic form. See, e.g., AMN1012; EX2022, ¶73. In
`
`contrast, another retinoid—tretinoin—has been successfully combined with at least
`
`four drugs for dermatological use. In 1999, tretinoin was successfully combined
`
`with mequinol to treat solar lentigines. AMN1037, 4-6. In 2002, tretinoin was
`
`combined with fluocinolone acetonide and hydroquinone to treat severe melasma.
`
`AMN1038, 3-6. In 2006 and 2010, tretinoin was combined with clindamycin
`
`phosphate for the treatment of acne vulgaris. AMN1039, 3-6; AMN1040, 3-6.
`
`Although not all of these products are indicated for the treatment of acne, they
`
`were all used to treat dermatological conditions, and tretinoin’s successful
`
`combination with multiple drugs would have made it a promising candidate for
`
`combination with dapsone.
`
`21. Consistent with my opinions above, Dr. Harper’s 2012 dapsone article
`
`instructs dermatologists in 2012 that dapsone is an effective acne treatment but
`
`says nothing of combining dapsone with adapalene (or any other drug). AMN1035,
`
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`

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`Inter Partes Review of U.S. Patent No. 9,161,926
`Second Declaration of Elaine S. Gilmore, M.D., Ph.D.
`(Exhibit 1034)
`5. In fact, the only reference to adapalene anywhere in Dr. Harper’s paper is the
`
`citation of Dr. Fleischer’s 2010 article which describes the co-administration of
`
`dapsone with multiple other separately formulated drugs, including adapalene—
`
`which confirms my opinion above. AMN1036, Abstract. Neither Dr. Harper’s
`
`2012 nor Dr. Fleischer’s 2010 article describes the use of dapsone in a combination
`
`product with adapalene. See AMN1035; AMN1036. In fact, Fleischer included
`
`specific instructions on separate dosing in order to avoid (minor) side effects from
`
`the separate administration of the two drugs. AMN1036, 13. In fact, Fleischer
`
`found that the incidence of side effects in co-administered dapsone/adapalene “was
`
`somewhat greater” than co-administered dapsone/benzoyl peroxide, and he
`
`attributed this greater incidence specifically to adapalene. AMN1036, 12. This
`
`finding undermines Dr. Harper’s reliance on side effects as a reason to select
`
`adapalene over other alternatives for combination with dapsone. EX2022, ¶168.
`
`*
`
`
`
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`Inter Partes Review of U.S Patent No. 9,161,926
`Second Declqrafion of Elaine S. Gilmore, M.D., Ph.D.
`(Exhibit 1034)
`I hereby declare that all statements made herein of my own knowledge are
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`true and that all statements made on information and belief are believed to be true,
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`and further that these statements were made with the knowledge that willful false
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`statements and the like so made are punishable by fure or imprisonment, or both,
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`under g l00l of title 18 of the United States Code.
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`Dated:3
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`\,\1c
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`f,laine S. Gilmore, M.D., Ph.D.
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`