GlaxoSmithKline Consumer Healthcare Holdings US LLC v. Cipla Ltd

1. Case Identification

• Case #: IPR2020-00368
• Patent #: 8,163,723
• Filed: January 31, 2020
• Petitioner(s): GlaxoSmithKline Consumer Healthcare Holdings (US), LLC
• Patent Owner(s): Cipla Ltd.
• Challenged Claims: 1-28

2. Patent Overview

• Title: Methods of Using Formulations of Azelastine and Fluticasone
• Brief Description: The ’723 patent claims methods for treating or preventing conditions like allergic rhinitis by intranasally administering a pharmaceutical composition that combines azelastine (an antihistamine) and fluticasone (a steroid).

3. Grounds for Unpatentability

Ground 1: Claims 1-28 are obvious over PDR 1999 in view of Segal.

• Prior Art Relied Upon: PDR 1999 (the Physicians' Desk Reference (1999)) and Segal (International Publication No. WO 98/48839).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that the combination was obvious because the individual components were well-known. PDR 1999 disclosed separate, FDA-approved, commercially successful nasal sprays for treating allergic rhinitis: Astelin®, containing azelastine hydrochloride, and Flonase®, containing fluticasone propionate. This establishes that each active ingredient was individually known to be safe and effective for intranasal treatment of the same condition. Segal taught pharmaceutical compositions for intranasal administration that explicitly combined a topical anti-inflammatory agent (disclosing fluticasone propionate as an example) with at least one additional therapeutic agent (disclosing azelastine as an example) for treating conditions like allergic rhinitis.
  • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA) would combine the known products from PDR 1999 based on the explicit teachings of Segal. Segal provided multiple rationales, including the convenience of a single composition, improved patient compliance, and the potential for "additive and synergistic effects." Furthermore, a POSA would recognize that azelastine and fluticasone have complementary mechanisms of action—the former treating the early-phase allergic reaction and the latter treating the late-phase reaction—providing a strong clinical motivation to combine them for optimal treatment.
  • Expectation of Success: A POSA would have had a high expectation of success. Both drugs were already known to be safe, effective, and administered via the same intranasal route for the same indication. Segal taught that such formulations could be prepared using standard techniques, and the ’723 patent itself concedes its formulations "are prepared by techniques well known in the art."
  • Key Aspects: The argument heavily relied on the fact that the prior art involved the exact same drugs, for the exact same indication, via the same route of administration, and that a separate reference explicitly suggested combining these specific classes of drugs for known benefits. Petitioner also detailed how various dependent claims were obvious, noting that PDR 1999 and Segal taught or suggested the claimed concentrations (e.g., 0.1% azelastine and 0.05% fluticasone), dosage forms (nasal spray), pH ranges (4.5-6.5), particle sizes (<10 µm), and the use of specific excipients like polysorbate 80, cellulose derivatives, and benzalkonium chloride.

Ground 2: Claims 1-28 are obvious over Cramer in view of PDR 1999.

• Prior Art Relied Upon: Cramer (European Patent Application Publication No. EP 0,780,127 A1) and PDR 1999.
• Core Argument for this Ground:
  • Prior Art Mapping: This ground presented an alternative, but similar, obviousness combination. Cramer disclosed pharmaceutical formulations for nasal administration comprising a glucocorticoid and a "leukotriene inhibiting antihistamine," explicitly naming fluticasone and azelastine as respective examples. The formulations were taught to be useful for treating allergic rhinoconjunctivitis. Cramer’s Example 3 described a co-formulation of azelastine HCl and a different steroid (triamcinolone acetonide) but stated that "substantially similar results are also obtained using...equivalent amounts of other glucocorticoid agents such as fluticasone." PDR 1999 again provided the real-world context of the specific, widely used Astelin® and Flonase® products.
  • Motivation to Combine: The motivation was intrinsic to Cramer, which taught that combining a nasal corticosteroid with an antihistamine like azelastine results in "improved intranasal compositions..., providing improved relief of symptoms." A POSA reading Cramer would be motivated to substitute the exemplified steroid with fluticasone, a well-known and preferred steroid for allergic rhinitis as shown in PDR 1999, to achieve the improved results taught by Cramer. The general motivations for combination therapy—complementary mechanisms and improved efficacy—also applied.
  • Expectation of Success: A POSA would have expected success for the same reasons as in Ground 1. Cramer explicitly stated that fluticasone was a suitable glucocorticoid for its combination therapy and that its formulations could be prepared using "conventional mixing techniques." Given that PDR 1999 established the safety and efficacy of intranasal fluticasone, a POSA would reasonably expect the combination taught by Cramer to be successful.
  • Key Aspects: This ground provided a more direct teaching of the combination, with Cramer identifying both classes of drugs and specifically naming azelastine and fluticasone as candidates. The argument for the dependent claims mirrored Ground 1, showing that Cramer and PDR 1999, along with general knowledge, disclosed the specific concentrations, excipients (e.g., polysorbate 80, benzalkonium chloride, glycerin), pH ranges, and aqueous suspension format recited in the dependent claims.

4. Arguments Regarding Discretionary Denial

• Petitioner argued that the petition should not be denied under 35 U.S.C. §325(d). Although Cramer was cited during prosecution, the patent owner overcame the rejection by arguing for objective indicia of nonobviousness. Petitioner contended these indicia were flawed and did not demonstrate nonobviousness.
• Petitioner also noted that a previous IPR on a related patent (the Argentum IPR) was instituted on similar grounds but was terminated by settlement before a final written decision. Therefore, the Board had not previously issued a substantive, final ruling on the patentability of the claims over the asserted art.

5. Relief Requested

• Petitioner requested institution of an inter partes review (IPR) and cancellation of claims 1-28 of Patent 8,163,723 as unpatentable.