Amneal Pharmceuticals LLC v. Almirall, LLC

1. Case Identification

• Case #: IPR2018-00608
• Patent #: 9,161,926
• Filed: February 12, 2018
• Petitioner(s): Amneal Pharmaceuticals LLC and Amneal Pharmaceuticals of New York, LLC
• Patent Owner(s): Allergan, Inc.
• Challenged Claims: 1-6

2. Patent Overview

• Title: Topical Dapsone Compositions
• Brief Description: The ’926 patent discloses topical pharmaceutical gel compositions for treating skin conditions. The claims are directed to an aqueous gel containing approximately 7.5% w/w dapsone, 30-40% w/w ethoxydiglycol as a solubilizing agent, and a specific acrylamide/sodium acryloyldimethyl taurate copolymer as a viscosity builder, while expressly excluding the compound adapalene.

3. Grounds for Unpatentability

Ground 1: Claims 1-6 are obvious over Garrett in view of Nadau-Fourcade.

• Prior Art Relied Upon: Garrett (WO 2009/061298) and Nadau-Fourcade (WO 2010/072958).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Garrett taught nearly all limitations of the challenged claims. Garrett disclosed a semi-solid aqueous gel for topical dapsone delivery, including a dapsone concentration range (5-10% w/w) that encompassed the claimed 7.5%, an overlapping ethoxydiglycol concentration range (10-30% w/w), and the presence of water. Garrett’s compositions also did not contain adapalene. The primary element missing from Garrett was the specific claimed acrylamide/sodium acryloyldimethyl taurate copolymer. Petitioner asserted that Nadau-Fourcade supplied this teaching, as it described this exact copolymer (e.g., Sepineo P 600) as a "preferred" gelling agent for topical formulations of water-insoluble drugs like dapsone. Petitioner further argued the claimed copolymer concentration (about 2-6% w/w) was obvious due to overlapping ranges in the prior art (Garrett: 0.2-4%, Nadau-Fourcade: 0.01-5%). Dependent claims adding methyl paraben were argued to be obvious as Garrett taught its use as a preservative.
  • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA) would combine Garrett and Nadau-Fourcade because both references address the same technical problem: creating stable topical formulations for water-insoluble active ingredients. Garrett disclosed a base dapsone composition and the need for a polymeric thickener. Nadau-Fourcade identified the specific claimed copolymer as a preferred, well-known, and interchangeable thickening agent suitable for such a composition, making its substitution into Garrett's formula a matter of predictable design choice.
  • Expectation of Success: A POSA would have a reasonable expectation of success in making the combination. All the components were known for use in topical formulations, were known to be compatible, and were used for their established functions. The prior art commercial product Aczone® Gel 5% had already successfully combined dapsone, ethoxydiglycol, and water, reinforcing the predictability of the claimed combination.

Ground 2: Claims 1-6 are obvious over Garrett in view of Bonacucina.

• Prior Art Relied Upon: Garrett (WO 2009/061298) and Bonacucina (AAPS PharmaSciTech, June 2009).
• Core Argument for this Ground:
  • Prior Art Mapping: As in Ground 1, Garrett provided the foundational dapsone gel composition. The challenge substituted Bonacucina for Nadau-Fourcade as the source for the claimed copolymer. Petitioner contended that Bonacucina, an in-depth study on the claimed copolymer (Sepineo P 600), taught that it was a "prime candidate" for formulating gels and emulsion gels with rheological properties suitable for topical administration. Bonacucina also disclosed that copolymer concentrations from 0.5% to 5% w/w were effective, overlapping with the claimed range.
  • Motivation to Combine: The motivation to combine was based on solving a known problem with prior art thickeners. Thickeners like Carbopol® 980 (used in the prior art Aczone® Gel 5% and taught by Garrett) were known to produce "gritty" compositions and required a harsh base (e.g., sodium hydroxide) for neutralization to function. Bonacucina taught that the claimed acrylamide copolymer provided smooth, stable gels and did not require neutralization. A POSA would therefore be motivated to substitute the copolymer from Bonacucina into Garrett’s dapsone composition to improve the final product's texture and feel ("smooth" vs. "gritty") and to simplify the manufacturing process by eliminating the neutralization step.
  • Expectation of Success: Success was reasonably expected because the combination involved substituting one known thickening agent for another to achieve a predictable improvement in cosmetic elegance and manufacturing efficiency. The known compatibility of the individual components, many of which were already used together in a commercial product, further supported this expectation.

4. Key Technical Contentions (Beyond Claim Construction)

• Rebuttal of "Unexpected Results": Petitioner argued that the Patent Owner's evidence of unexpected results submitted during prosecution was flawed. The alleged incompatibility of Carbopol® 980 with 40% ethoxydiglycol was irrelevant because Carbopol is not a claimed element, and thus the comparison lacks nexus to the claims. Furthermore, Petitioner contended that any observed reduction in dapsone particle size when using the claimed copolymer was a predictable difference in degree, not an unexpected difference in kind, as the prior art taught that the choice of thickener affects particle dispersion and that formulation process variables can be adjusted to control particle size.

5. Arguments Regarding Discretionary Denial

• Denial under §325(d) is Inappropriate: Petitioner argued against discretionary denial because the core prior art references (Garrett, Nadau-Fourcade, and Bonacucina) were not before the examiner during the original prosecution. Therefore, the patentability of the claims had not been tested against this specific and more relevant art. Petitioner also asserted that its grounds presented motivations to combine that were more specific and compelling than the general "functional equivalents" reasoning relied upon by the examiner, particularly the motivation in Ground 2 to solve the known "grittiness" and neutralization issues associated with Carbopol-based gels.

6. Relief Requested

• Petitioner requested the institution of an inter partes review and the cancellation of claims 1-6 of Patent 9,161,926 as unpatentable under 35 U.S.C. §103.