Petition for Inter Partes Review of U.S. Patent No. 9,517,219 “[i]n recent years, there has been great interest in the use of novel polymers with complex functions as emulsifiers and thickeners because the gelling capacity of these compounds allows the formulation of stable emulsions and creams by decreasing surface and interfacial tension and at the same time increasing the viscosity of the aqueous phase.” (MYLAN1015, 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 topical pharmaceutical composition comprising: [a] about 7.5% w/w dapsone; [b] about 30% w/w to about 40% w/w diethylene glycol monoethyl ether; [c] about 2% w/w to about 6% w/w of a polymeric viscosity builder consisting of acrylamide/sodium acryloyldimethyl taurate copolymer; [d] and water; Petition for Inter Partes Review of U.S. Patent No. 9,517,219 Garrett: “In one preferred embodiment, the composition includes about 0.5% to 4.0% carbomer; about 53.8% to 84.2% water; about 10% to 30% ethoxydiglycol; about 0.2% methylparaben; about 5% to 10% dapsone in a microparticulate and dissolved state; and about 0.1% to 2% sodium hydroxide solution.” (MYLAN1004, 4:2-5) Garrett: “In one preferred embodiment, the composition includes about 0.5% to 4.0% carbomer; about 53.8% to 84.2% water; about 10% to 30% ethoxydiglycol; about 0.2% methylparaben; about 5% to 10% dapsone in a microparticulate and dissolved state; and about 0.1% to 2% sodium hydroxide solution.” (MYLAN1004, 4:2-5) Garrett: “Thickening agents include polymer thickeners.

Polymer thickeners that may be used include those known to one skilled in the art, such as hydrophilic and hydroalcoholic gelling agents frequently used in the cosmetic and pharmaceutical industries.” (MYLAN1004, 13:3-5) Bonacucina: “Preferably, the gelling agent comprises between about 0.2% to about 4% by weight of the composition.” (MYLAN1004, 13:10-11) “Sepineo® P 600, based on the concept of droplet hydroswelling, is a concentrated droplet dispersion of acrylamide/sodium acryloyldimethyl taurate (a viscous liquid at room temperature) in isohexadecane as the oily Petition for Inter Partes Review of U.S. Patent No. 9,517,219 dispersing phase.” (MYLAN1015, 2; MYLAN1002/1035, ¶70) “Both techniques revealed that Sepineo® P 600 thickens and gels well, a property that depends strongly on polymer concentration.

Petition for Inter Partes Review of U.S. Patent No. 9,517,219 A POSA would understand that small variations in the preparation of the composition can affect the properties (e.g., particle size, polymorph) of a resulting recrystallized precipitate.

The examiner previously considered Garrett as a secondary reference in the context of two dependent claims for the limited proposition that topical dapsone formulations had been shown to be effective in the treatment of acne vulgaris.

133 (2011) (“Fabbrocini”) Zoe D. Draelos et al., Two randomized studies demonstrate the efficacy and safety of dapsone gel, 5% for the treatment of acne vulgaris, 46 J. Am. Acad. Dermatol.

783 (2011) (“Tanghetti”) Diane Thiboutot et al., An aqueous gel fixed combination of clindamycin phosphate 1.2% and benzoyl peroxide 2.5% for the once-daily treatment of moderate to severe acne vulgaris: Assessment of efficacy and safety in 2813 patients, 59 J. Am. Acad. Dermatol.

Exhibit No. 2060 Description M. P. Heffernan et al., A Pilot Study of the Safety and Efficacy of Picolinic Acid Gel in the Treatment of Acne Vulgaris, 156 British J. Dermatol.

548 (2006) (“Heffernan”) Janusz Marcinkiewicz et al., Topical Taurine Bromamine, a New Candidate in the Treatment of Moderate Inflammatory Acne Vulgaris - A Pilot Study, 18 Eur.

41 (2012) (“Chang”) Supplemental Declaration of David W. Osborne, Ph.D. (served August 30, 2019) Erick H. Turner, How to access and process FDA drug approval packages for use in research, BMJ (2013) ("Turner 2013") (served August 30, 2019) Manual of Policies and Procedures - Center for Drug Evaluation and Research (served August 30, 2019) Transcript of Deposition of Bozena B. Michniak-Kohn, Ph.D., FAAPS, M.R.Pharm.S., dated December 6, 2019 Transcript of Deposition of Elaine S. Gilmore, M.D., Ph.D., dated December 12, 2019 Transcript of PTAB Conference Call, dated January 17, 2020 2061 2062 2063 2064 2065 2066 2067 2068 2069 2070

Amneal Exhibit # 1019 1020 1021 1022 1023 1024 1025 1026 1027 1028 1029 1030 1031 1032 1033 Description Curriculum Vitae for Elaine S. Gilmore, M.D., Ph.D. Affidavit of Christopher Butler Intentionally left blank Wozel, D., “Innovative Use of Dapsone” Dermatol.

46: 697- 712 (2007) (“Thiboutot”) Nguyen, R. and Su, J., “Treatment of Acne Vulgaris” Pediatrics and Child Health 21: 119-125 (2010) (“Nguyen”) Williams, H., et al., “Acne vulgaris” Lancet 379: 361–72 (2012) (“Williams”) Sepineo™ P 600 Brochure Barclay, L., “Use of Topical Corticosteroids for Dermatologic Conditions Reviewed” Medscape - Jan 21, 2009, accessed from https://www.medscape.com/viewarticle/587159_print (“Barclay”) 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.

Male Patients With Facial Acne Vulgaris: Gender as a Clinically Relevant Outcome Variable,” Journal of Drugs in Dermatology 11:1417-1421 (2012) Intentionally left blank Neutralizing Carbopol® and Pemulen® Polymers in Aqueous and Hydroalcoholic Systems, published January 2002 (“Noveon Technical Data Sheet”) 2010 Inactive Ingredient Database, available at: http://wayback.archive-it.org/7993/20170112022245/http:/www.fda.

Sullivan, D., et al., “A review of the nonclinical safety of Transcutol®, a highly purified form of diethylene glycol monoethyl ether (DEGEE) used as a pharmaceutical excipient,” Food and Chemical Toxicology 72: 4-50 (2014) FDA Inactive Ingredient Database Field Descriptions Andersson, D., “Evonik-Degussa expands its cooperation with Alsiano,” Pharma & Healthcare News 7:1-10 (2007) File History of U.S. Patent No. 9,161,926 Deposition Transcript for Julie C. Harper, M.D., Case IPR2018- 00608 (March 11, 2019) 1045 1046 1047 1048 1049 1050 1051 1052 1053 1054 1055 1056 1057 Case IPR2019-00207 Patent 9,517,219 B2

Amneal Exhibit # Description 1079 Emails dated from December 31, 2019 to January 23, 2020 between James Trainor, Adam LaRock, Elizabeth Hagan, RJ Shea, Dennies Varughese, and Tyler Liu regarding the confidentiality of Dr. Warner’s deposition transcript [REDACTED] Deposition Transcript of Kevin Warner, Allergan, Inc. v. Taro Pharmaceutical Industries Ltd., and Taro Pharmaceuticals Inc., Civil Action No. 17-663 (D.Del. July 18, 2018) 10252301_1.docx 1080

Pursuant to 37 C.F.R. § 42.70(a) and the Scheduling Order dated May 10, 2019 (Paper 14), Patent Owner Almirall, LLC respectfully submits this Request for Oral Argument.

The patentability of the challenged claims over the combination of Garrett (Ex. 1004) and Bonacucina (Ex. 1015); c. Any issues identified in Petitioner’s Request for Oral Argument; d. Rebuttal to Petitioner’s presentation on all matters; e. Any other issues raised in papers filed in this proceeding, including issues raised in papers yet to be filed or filed concurrently; and f. Any additional issues on which the Board seeks information or clarification.

Patent Owner further requests permission to use audio/visual equipment at the oral argument, including a computer, projector, and screen for displaying demonstratives and/or exhibits.

Patent Owner requests sixty (60) minutes to present its arguments.

Respectfully submitted, FENWICK & WEST LLP By:/James S. Trainor/ James S. Trainor (Reg. No. 52,297) Attorneys for Patent Owner Almirall, LLC

Case IPR2019-00207 Patent 9,517,219 B2 Pursuant to the Board’s May 10, 2019 Scheduling Order (Paper 14), Petitioners Amneal Pharmaceuticals LLC and Amneal Pharmaceuticals of New York, LLC respectfully request oral argument, currently scheduled for February 7, 2020.

Petitioners request one hour in which to present their arguments.

Any issue discussed in the Board’s Institution Decision (Paper 13).

Petitioners also respectfully request access to the Board’s audio-visual equipment to display demonstrative exhibits, including a projector and screen for displaying documents from a computer.

Lead Counsel for Petitioners Registration No. 61,868 CERTIFICATE OF SERVICE (37 C.F.R. § 42.6(e)) The undersigned hereby certifies that the above-captioned “Petitioners’ Request for Oral Argument” was served in its entirety on December 20, 2019, via electronic mail upon the following counsel for Patent Owner: James Trainor Elizabeth B. Hagan Richard J. Shea

Mail Stop "PATENT BOARD" Patent Trial and Appeal Board U.S. Patent and Trademark Office P.O.

Box 1450 Alexandria, VA 22313-1450

Notice of Stipulation to Extend Due Dates 1, 2, and 3 Pursuant to the May 10, 2019 Scheduling Order (Paper 14) and the Notice of Stipulation to Extend Due Dates 1, 2, and 3 (Paper 19), Patent Owner Almirall LLC hereby provides notice that Petitioners and Patent Owner have stipulated and agreed to further extend Due Date 3 as shown in bold type below.

Respectfully submitted,

Attorneys for Patent Owner Almirall, LLC

Notice of Deposition of Dr. Gilmore

PLEASE TAKE NOTICE that pursuant to 37 C.F.R. § 42.53, Patent Owner Almirall, LLC will take the deposition of Petitioners’ declarant, Dr. Elaine S. Gilmore, M.D., Ph.D. upon oral examination as follows.

Location: Sterne, Kessler, Goldstein & Fox P.L.L.C. 1100 New York Avenue NW Washington, DC 20005 The deposition will be recorded by stenographic and/or audio means by a court reporter licensed to administer oaths.

Respectfully submitted, FENWICK & WEST LLP By: /James Trainor/ James Trainor (Reg. No. 52,297)

Attorneys for Patent Owner Almirall, LLC

Pursuant to 37 C.F.R. § 42.10(c), and as authorized in the Board’s Notice of Filing Date issued November 14, 2018 (Paper 4), Patent Owner Almirall, LLC (“Almirall”) respectfully requests the pro hac vice admission of Elizabeth B. Hagan in this proceeding.

She represented Patent Owner Almirall, LLC in the district court litigation against Taro Pharmaceutical Industries Ltd. that terminated March 11, 2019.

As trial counsel for Almirall, LLC, Ms. Hagan was actively involved in all aspects of the district court litigation, including development of validity positions regarding the patent challenged in this proceeding.

Ms Hagan has also applied to appear pro hac vice before the Office in Eli Lilly and Co. v. Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, IPR2014-00752.

Motion for Admission Pro Hac Vice familiarity with the subject matter at issue in this proceeding, including the ’219 patent, the parties’ written submissions, and the cited references.

Patent Owner.

PLEASE TAKE NOTICE that pursuant to 37 C.F.R. § 42.53, Patent Owner Almirall, LLC will take the deposition of Petitioners’ declarant, Dr. Bozena B. Michniak-Kohn, upon oral examination as follows.

Location: Norris McLaughlin P.A. 400 Crossing Boulevard Bridgewater, NJ 08807 The deposition will be recorded by stenographic and/or audio means by a court reporter licensed to administer oaths.

Respectfully submitted, FENWICK & WEST LLP By: /James Trainor/ James Trainor (Reg. No. 52,297)

Attorneys for Patent Owner Almirall, LLC

Patent Owner’s Updated Mandatory Notices Under 37 C.F.R. § 42.8

Pursuant to 37 C.F.R. § 42.8, Patent Owner, Almirall, LLC (“Almirall”), hereby files the following updated mandatory notices.

Dated: November 19, 2019 Respectfully submitted,

Reg. No. 52,297 Counsel for Almirall, LLC Patent Owner’s Updated Mandatory Notices Under 37 C.F.R. § 42.8

Moreover, Almirall’s arguments raise material factual disputes as to whether Amneal’s cited art overcomes Almirall’s alleged unexpected results evidence, further compelling institution of the IPR.

The Board typically exercises its discretion under § 314(a) and the General Plastic factors to deny institution of “follow-on” IPRs that are duplicative of earlier-filed petitions on the same patent, to avoid offending notions of res judicata, judicial economy, and petitioner diligence.

Almirall also ignores that in a parallel district court litigation over the ’219 patent—where Amneal was not a party—claim construction of the term “polymeric viscosity builder” was outstanding prior to this Petition.

Factors 6 and 7 also do not warrant denying institution because the Petition is not a serial attack on the same patent that imposes any inefficient and uneconomical “tax” on the Board.

At bottom, Almirall’s analysis of Becton factor (f) asks this Board to make factual findings as to whether the Petition “warrant[s] reconsideration” of alleged unexpected results.

Patent Owner’s Objections to Reply Evidence finding that Exhibit 1045 “is what [Amneal] claims it is.” See FRE 901.

Patent Owner’s Objections to Reply Evidence consequence in determining this action more or less probable than it would be without this exhibit.

Patent Owner’s Objections to Reply Evidence states on its face that “no representations… of any kind are made as to [the] accuracy” of the information contained therein.

Exhibit 1052 appears to be a printout of a portion of a spreadsheet titled “3Q2018EXCEL,” and Amneal’s expert Dr. Michniak-Kohn describes it as “the FDA DMF database that [she] downloaded” from a particular weblink.

Amneal relies on Exhibit 1075 only as a seventh source to support the sentence “a POSA would have known that Aczone 5% Gel contained undissolved dapsone before 2012.” Paper 28 at 9–10.

Description Curriculum Vitae for Elaine S. Gilmore, M.D., Ph.D. Affidavit of Christopher Butler Intentionally left blank Wozel, D., “Innovative Use of Dapsone” Dermatol.

46: 697- 712 (2007) (“Thiboutot”) Nguyen, R. and Su, J., “Treatment of Acne Vulgaris” Pediatrics and Child Health 21: 119-125 (2010) (“Nguyen”) Williams, H., et al., “Acne vulgaris” Lancet 379: 361–72 (2012) (“Williams”) Sepineo™ P 600 Brochure Barclay, L., “Use of Topical Corticosteroids for Dermatologic Conditions Reviewed” Medscape - Jan 21, 2009, accessed from https://www.medscape.com/viewarticle/587159_print (“Barclay”) 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.

Amneal Exhibit # Description Inactive Ingredient Search for Approved Drug Products: Frequently Asked Questions, Retrieved from https://www.fda.gov/drugs/drug- approvals-and-databases/inactive-ingredient-search-approved-drug- products-frequently-asked-questions#inactive%20as%20active?, last accessed on October 25, 2019 Lubrizol Technical Data Sheet, Dispersion Techniques for Carbopol® Polymers Kircik, L.H., “Use of Dapsone 5% Gel as Maintenance Treatment of Acne Vulgaris Following Completion of Oral Doxycycline and Dapsone 5% Gel Combination Treatment,” Journal of Drugs in Dermatology 15(2):191-195 (2016) Tanghetti, E., et al., “The Efficacy and Tolerability of Dapsone 5% 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) Intentionally left blank Neutralizing Carbopol® and Pemulen® Polymers in Aqueous and Hydroalcoholic Systems, published January 2002 (“Noveon Technical Data Sheet”) 2010 Inactive Ingredient Database, available at: http://wayback.archive-it.org/7993/20170112022245/http:/www.fda.

Sullivan, D., et al., “A review of the nonclinical safety of Transcutol®, a highly purified form of diethylene glycol monoethyl ether (DEGEE) used as a pharmaceutical excipient,” Food and Chemical Toxicology 72: 4-50 (2014) FDA Inactive Ingredient Database Field Descriptions Andersson, D., “Evonik-Degussa expands its cooperation with Alsiano,” Pharma & Healthcare News 7:1-10 (2007) File History of U.S. Patent No. 9,161,926 Deposition Transcript for Julie C. Harper, M.D., Case IPR2018- 00608 (March 11, 2019) 1045 1046 1047 1048 1049 1050 1051 1052 1053 1054 1055 1056 1057

), 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”) File History of U.S. Patent No. 9,517,219 Declaration of Elaine S. Gilmore, M.D., Ph.D.

Description Curriculum Vitae for Elaine S. Gilmore, M.D., Ph.D. Affidavit of Christopher Butler Intentionally left blank Wozel, D., “Innovative Use of Dapsone” Dermatol.

28: 599– 610 (2010) (“Wozel”) Thiboutot, D., et al., “Pharmacokinetics of Dapsone Gel, 5% for the Treatment of Acne Vulgaris” Clin.

46: 697- 712 (2007) (“Thiboutot”) Nguyen, R. and Su, J., “Treatment of Acne Vulgaris” Pediatrics and Child Health 21: 119-125 (2010) (“Nguyen”) Williams, H., et al., “Acne vulgaris” Lancet 379: 361–72 (2012) (“Williams”) Sepineo™ P 600 Brochure Barclay, L., “Use of Topical Corticosteroids for Dermatologic Conditions Reviewed” Medscape - Jan 21, 2009, accessed from https://www.medscape.com/viewarticle/587159_print (“Barclay”) 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.

CERTIFICATE OF SERVICE (37 C.F.R. § 42.6(e), 42.105(a)) The undersigned hereby certifies that the above-captioned “Petitioners’ Exhibit List”, along with exhibits 1035 – 1038, were served in their entirety on October 18, 2019, via electronic mail upon the following counsel for Patent Owner: