Not only does this mean that Almirall did not satisfy its threshold obligation, but failing to timely Case IPR2019-00207 Patent 9,517,219 B2 object deprived Amneal an opportunity to cure any issue.

Because Almirall failed to diligently review the declarations of Dr. Michniak-Kohn and Dr. Gilmore and file any objections within five business days, Almirall’s motion to exclude should be denied on this basis alone.

Case IPR2019-00207 Patent 9,517,219 B2 Almirall’s sole complaint is that Dr. Michniak-Kohn and Dr. Gilmore relied on factual information supplied by counsel concerning the deposition statements and admissions by Almirall’s declarants.

Moreover, the information supplied by counsel is nothing more than confirmatory evidence that supports the already-stated opinions of Dr. Michniak-Kohn and Dr. Gilmore based on those expert’s view of the published literature and prior art, their own experience, and their own understanding of the technical field.

In fact, Almirall spent much time at both depositions examining the witness on the published literature and prior art, their own experience, and their own understanding of the technical field.

Pursuant to 35 U.S.C. §§ 141(c), 142, and 319 and 37 C.F.R.§§ 90.2(a) and 90.3(b)(1), Patent Owner Almirall, LLC (“Almirall”) hereby provides notice that it appeals to the United States Court of Appeals for the Federal Circuit from the Final Written Decision entered on May 29, 2020 (Paper 58, attached hereto as Appendix A) in IPR2019-00207 before the Patent Trial and Appeal Board regarding the inter partes review of U.S. Patent No. 9,517,219 (“the ’219 patent”), and from all underlying findings, determinations, orders, decisions, rulings, and opinions, including Almirall’s Request for Rehearing (Paper 61), which was denied on July 23, 2020 (Paper 62).

In accordance with 37 C.F.R. § 90.2(a)(3)(ii), Almirall states that the issues on appeal include, but are not limited to: 1.

Whether the Board erred in finding that claims 1–8 of the ’219 patent are unpatentable under 35 U.S.C. § 103(a) over the combination of two references: (1) Garrett; and (2) Giulia Bonacucina et al., Characterization and Stability of Emulsion Gels Based on Acrylamide/Sodium Acryloyldimethyl Taurate Copolymer, 10(2) AAPS PHARMSCITECH 368–75 (2009) (Ex. 1015, “Bonacucina”); 3.

Whether the Board erred in any finding relating to the aforementioned claims and grounds, including the scope and content of the prior art; and 4.

Whether the Board erred in any other issues decided adversely to Almirall in any order, decision, ruling or opinion.

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 1045 1046 1047 1048 1049 1050 1051 1052 1053 1054 1055 1056 1057 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)

Pursuant to 37 C.F.R. § 42.64(c), Patent Owner Almirall, LLC (“Almirall”) moves to exclude from evidence portions of Exhibits 1043 and 1044, the second declarations of Petitioners’ experts Drs.

 “Bonacucina also discloses that Sepineo can be easily rubbed into the skin, which I understand Dr. Osborne also agreed at his deposition is needed for acne treatments that are applied topically to the face, like dapsone.” Id. ¶ 59.

Thus, even if a POSA was discouraged from utilizing a suspension formulation, she could completely dissolve the dapsone, as taught by Garrett, to avoid Ostwald ripening issues.” Id. ¶ 78.

 “I understand that Dr. Kircik testified that he frequently used dapsone to treat rosacea if other FDA-approved treatments, such as metronidazole or azelaic acid, failed for a particular patient or

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

If the exhibits and paragraphs identified herein remain in the record, Almirall could continue to rely upon them on appeal, and Amneal would be unfairly forced to address them again.

To date, Amneal has not had an opportunity to subject the declarant (Dr. Warner) to cross examination.1 This is important because the Board previously found that it was beyond speculation that something useful would be discovered from Dr. Warner’s deposition.

This prejudice is entirely of Almirall’s making, as it has been aware that Amneal sought Dr. Warner’s deposition since September 2019 yet appears to have first contacted the witnesses eight days after the Board’s December 31 order.

But the Warner Declaration has critical flaws: (1) it does not disclose what is meant by Dr. Warner’s statement that the prior art dapsone compositions show purported “undesired polymer aggregates” or the basis on which that determination was made, and (2) it does not disclose how the dapsone compositions described in the Warner Declaration were prepared even though the prior art informs that the preparation method will impact both polymer aggregation and particle size.

Even if Dr. Osborne’s opinions on purported unexpected results are not excluded, such expert testimony that does not disclose the underlying facts or data is entitled to “little or no weight.” See 37 CFR § 42.65(a).

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.

Certainly, Petitioners provide nothing in reply to cure the infirmity of their asserted evidence that there existed a credible motivation to use the claimed A/SA copolymer-based polymeric viscosity builder (“PVB”), let alone to combine either Nadau-Fourcade or Bonacucina with Garrett.

As such, the record evidence remains explicit and unanswered that prior art published closely in time to the invention date taught that dapsone should be used in combination with another API, and with adapalene specifically.

Petitioners’ reliance on conclusory statements such as “thickening agents were known to be interchangeable and predictable” (Petition at 31) and “this Sepineo that’s easy to use…” (see generally, Ex. 2063 at 207:6–209:14) does not meet their burden or overcome the overwhelming evidence of the complexity involved in drug formulation.

Most critically, Petitioners cannot point to a single prior art reference that marginally relates—or even discloses, however disparately, within the same four corners—the three components that define the compositions recited in the challenged claims: dapsone, DGME, and an A/SA-based PVB.

But even setting them aside, Almirall has not offered any legal or factual arguments to overcome the clear prima facie obviousness case here on the merits, particularly regarding reasons to combine Garrett with Nadau-Fourcade or Bonacucina.

For Ground 2, a POSA would have been separately motivated to replace Carbopol® in Garrett’s formulation with Sepineo® because using Carbopol® required additional hydration and neutralization steps, and also because Carbopol® yielded an unpleasant gritty texture in the commercial Aczone 5% Gel.

Garrett explains that Aczone 5% Gel was “developed to deliver therapeutic concentrations of dapsone to the skin,” and resulted in a 44% and 5% reduction in inflammatory and non-inflammatory acne lesions respectively.4 AMN1004, 4:9-15, selecting a “more reasonable” starting compound.

BTG Int’l Ltd. v. Amneal Pharm. LLC, 923 F.3d 1063, 1076 (Fed. Cir. 2019) (“lack of enthusiasm by a few is not equivalent to skepticism 5 Dr. Kircik received more than $100,000 from Allergan for, inter alia, promotional speaking engagements to inform and educate peers on the benefits of ACZONE® Gel 5%.

And Garrett also taught a POSA that the amounts of dissolved and undissolved dapsone in the composition could be modified to provide minimum (or maximum) reservoir capacity and thereby maintain sustained drug delivery.

Pursuant to 37 C.F.R. § 42.10(c), and as authorized in the Board’s Notice of Filing Date issued June 10, 2019 (Paper 5), Patent Owner Almirall, LLC (“Almirall”) respectfully requests the pro hac vice admission of Elizabeth B. Hagan in this proceeding.

As trial counsel for Almirall, LLC, Ms. Hagan has been actively involved in all aspects of the district court litigations, 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,

Based on the facts contained herein, as supported by Ms. Hagan’s declaration (Ex. 2001), good cause exists to admit Ms. Hagan pro hac vice in this proceeding.

Motion for Admission Pro Hac Vice Dated: July 2, 2019 Respectfully submitted, FENWICK & WEST LLP By: /James Trainor/ James Trainor (Reg. No. 52,297) Attorneys for Patent Owner Almirall, LLC

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.