Argentum Pharmaceuticals LLC v. Cipla Ltd

1. Case Identification

• Case #: IPR2017-00807
• Patent #: 8,168,620
• Filed: February 2, 2017
• Petitioner(s): Argentum Pharmaceuticals LLC
• Patent Owner(s): Cipla Ltd.
• Challenged Claims: 1, 4-6, 24-26, 29, and 42-44

2. Patent Overview

• Title: Combination of Azelastine and Steroids
• Brief Description: The ’620 patent discloses pharmaceutical formulations for nasal administration that combine azelastine (an antihistamine) and a pharmaceutically acceptable ester of fluticasone (a corticosteroid) to treat allergy-related conditions like allergic rhinitis.

3. Grounds for Unpatentability

Ground 1: Anticipation over Segal - Claims 1 and 25 are anticipated by Segal

• Prior Art Relied Upon: Segal (International Publication No. WO 98/48839).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Segal, published in 1998, discloses every element of claims 1 and 25. Segal describes topically applicable nasal compositions comprising an anti-inflammatory agent and an antihistamine. Critically, Segal identified fluticasone propionate as a preferred anti-inflammatory agent and azelastine as a suitable antihistamine. Segal also taught that these compositions could be formulated as nasal sprays containing a pharmaceutically acceptable carrier, such as a water-buffered aqueous solution.
  • Key Aspects: Petitioner contended that Segal’s disclosure of a limited number of preferred anti-inflammatories and suitable antihistamines (54 total combinations) made the specific combination of fluticasone propionate and azelastine readily envisioned by a Person of Ordinary Skill in the Art (POSA), satisfying the standard for anticipation.

Ground 2: Obviousness over Core Combination - Claims 1, 4-6, 24-26, and 29 are obvious over Hettche, Phillipps, and Segal

• Prior Art Relied Upon: Hettche (Patent 5,164,194), Phillipps (Patent 4,335,121), and Segal (WO 98/48839).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner asserted that the challenged claims represented a simple, predictable combination of known elements. Hettche taught the use of azelastine in a nasal spray for treating allergic rhinitis (the basis for the commercial product Astelin®). Phillipps taught the use of fluticasone propionate, a specific ester of fluticasone, for nasal administration to treat rhinitis (the basis for Flonase®). Segal explicitly taught combining an anti-inflammatory like fluticasone with an antihistamine like azelastine. Dependent claims reciting specific concentrations (claims 5, 6, 26) and particle sizes (claim 4) were also disclosed or suggested by Hettche and Phillipps, which described ranges that overlap or are identical to those claimed.
  • Motivation to Combine: A POSA would combine these references for several reasons. First, Segal provided an express motivation to co-formulate the agents to improve patient compliance by avoiding the inconvenience of administering multiple separate sprays. Second, clinical guidelines at the time recommended combination therapy with nasal corticosteroids and antihistamines for patients with inadequate symptom control. Third, a POSA would have sought to leverage the known complementary mechanisms of action: azelastine's rapid onset and fluticasone's long-term efficacy.
  • Expectation of Success: A POSA would have had a high expectation of success because combining the two active ingredients, both already successfully formulated in commercial aqueous nasal sprays, would have involved known formulation techniques to achieve a predictable result.

Ground 3: Obviousness over Core Combination plus Excipients - Claims 42-44 are obvious over Hettche, Phillipps, Segal, and Flonase® Label

• Prior Art Relied Upon: Hettche (Patent 5,164,194), Phillipps (Patent 4,335,121), Segal (WO 98/48839), and the Flonase® Label (1998).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground built upon the combination in Ground 2, arguing that the addition of specific excipients recited in dependent claims 42-44 was obvious. These claims add common pharmaceutical excipients, including edetate disodium, glycerine, microcrystalline cellulose, polysorbate 80, and benzalkonium chloride. Petitioner argued that these excipients were all present in the commercial Flonase® formulation (as shown on its label) or taught for use with azelastine in Hettche.
  • Motivation to Combine: A POSA tasked with creating a stable and effective co-formulation would have been motivated to use the very same excipients already proven to be safe and effective in the individual commercial products (Flonase® and Astelin®). Using these known components for their established functions (e.g., as preservatives, suspending agents, surfactants) would have been a routine and obvious design choice.
  • Expectation of Success: Because the excipients were known to be compatible with both active drugs and were used for the same functions as in the individual formulations, a POSA would have reasonably expected to successfully combine them into a single, stable nasal spray.

4. Key Claim Construction Positions

• Petitioner proposed that the term "conditions" (from claim 24) should be construed as "disease(s) or illness(es)". This construction was argued to be consistent with the patent specification, which discusses treating "allergy-related conditions" such as allergic rhinitis, and was also consistent with a construction adopted in a related district court case. This broader construction prevents the patent owner from narrowly limiting the claims to "allergic reactions" and supports the applicability of prior art references that treat general nasal inflammatory conditions.

5. Key Technical Contentions (Beyond Claim Construction)

• Petitioner argued that the ’620 patent was not entitled to its claimed foreign priority date (June 14, 2002), and that its effective filing date for certain claims was no earlier than the PCT filing date (June 13, 2003). The argument centered on the priority application’s alleged failure to provide adequate written description for the broad genus term "pharmaceutically acceptable ester of fluticasone." Petitioner contended the priority document disclosed only one specific ester (fluticasone propionate) and provided no guidance to define the full scope of the claimed genus, thus failing to demonstrate that the inventor possessed the full genus at the time of the priority filing.

6. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under 35 U.S.C. §325(d) was inappropriate. It was asserted that this was the first time the ’620 patent had been challenged in an IPR. More importantly, the primary prior art references relied upon in the petition—Segal, Hettche, Phillipps, and the Flonase® Label—were never cited or considered by the examiner during the original prosecution. Therefore, the petition presented new arguments and art that raised substantial new questions of patentability.

7. Relief Requested

• Petitioner requested the institution of an inter partes review and cancellation of claims 1, 4-6, 24-26, 29, and 42-44 of the ’620 patent as unpatentable.