Alcon Research Ltd v. Lupin Ltd

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Alcon Research, Ltd. (Delaware)
  • Defendant: Lupin Ltd. (India) and Lupin Pharmaceuticals, Inc. (Delaware)
  • Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP; Williams & Connolly LLP
• Case Identification: 1:17-cv-00321, D. Del., 03/24/2017
• Venue Allegations: Plaintiff alleges venue is proper in Delaware as Defendant Lupin Pharmaceuticals, Inc. is a Delaware corporation and both Defendants transact business, have engaged in systematic and continuous business contacts within the state, and have previously availed themselves of the district's courts.
• Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the PAZEO® ophthalmic solution constitutes an act of infringement of a patent covering a high-concentration olopatadine formulation.
• Technical Context: The technology concerns pharmaceutical compositions for ophthalmic use, specifically stable, high-concentration formulations of the antihistamine olopatadine for treating ocular allergic conjunctivitis.
• Key Procedural History: The lawsuit was initiated under the Hatch-Waxman Act, triggered by a Notice Letter from Lupin dated March 15, 2017. This letter informed Alcon of Lupin's ANDA filing, which included a Paragraph IV certification asserting that U.S. Patent No. 9,533,053 is invalid, unenforceable, or will not be infringed by Lupin's proposed generic product.

Case Timeline

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 9,533,053 - “High Concentration Olopatadine Ophthalmic Composition,” Issued January 3, 2017

The Invention Explained

• Problem Addressed: The patent addresses the technical challenge of creating a stable, comfortable ophthalmic solution containing a high concentration of the drug olopatadine ('053 Patent, col. 2:1-8). While lower-concentration olopatadine solutions were known to treat early-phase allergy symptoms, a higher concentration was desired to also treat more persistent late-phase symptoms. However, olopatadine has poor water solubility, making it "extremely difficult and complex" to create a high-concentration, stable formulation ('053 Patent, col. 1:24-34; col. 2:1-4).
• The Patented Solution: The invention is a specific aqueous formulation that successfully solubilizes a high concentration of olopatadine. It achieves this by combining the drug with a specific set of excipients: a polyether (polyethylene glycol, or PEG), a lactam polymer (polyvinylpyrrolidone, or PVP), and a particular type of cyclodextrin derivative, which together enhance and maintain the solubility of the olopatadine ('053 Patent, col. 2:46-62). This combination is described as overcoming the stability and solubility issues that prevented the development of such a high-concentration product ('053 Patent, col. 5:59 - col. 6:3).
• Technical Importance: This formulation enabled the development of an ophthalmic solution with sufficient olopatadine concentration to provide relief from both early-phase and late-phase symptoms of ocular allergic conjunctivitis, potentially with a more convenient once-a-day dosing schedule ('053 Patent, col. 1:45-58).

Key Claims at a Glance

• The complaint asserts infringement of independent claims 1 and 8, and reserves the right to assert additional claims (Compl. ¶ 31).
• Independent Claim 1:
  • An aqueous ophthalmic solution for treatment of ocular allergic conjunctivitis, comprising:
  • at least 0.67 w/v % olopatadine dissolved in the solution;
  • PEG having a molecular weight of 200 to 800;
  • polyvinylpyrrolidone;
  • a cyclodextrin selected from the group consisting of SAE-β-cyclodextrin, hydroxypropyl-β-cyclodextrin and hydroxypropyl-γ-cyclodextrin; and
  • water.
• Independent Claim 8:
  • An aqueous ophthalmic solution for treatment of ocular allergic conjunctivitis, the solution comprising:
  • at least 0.67 w/v % olopatadine dissolved in the solution;
  • PEG having a molecular weight of 200 to 800;
  • polyvinylpyrrolidone;
  • a cyclodextrin selected from the group consisting of hydroxypropyl-β-cyclodextrin and hydroxypropyl-γ-cyclodextrin;
  • benzalkonium chloride;
  • hydroxypropylmethyl cellulose; and
  • water.

III. The Accused Instrumentality

Product Identification

The accused instrumentality is "Lupin's ANDA Product," a generic olopatadine ophthalmic solution described in Abbreviated New Drug Application No. 208896 submitted to the FDA (Compl. ¶ 2).

Functionality and Market Context

The complaint alleges that Lupin's ANDA Product is a generic version of Alcon's branded PAZEO® ophthalmic solution and contains the "same or equivalent ingredients in the same or equivalent amounts" (Compl. p. 2:1-3). The filing of the ANDA is a statutory act of infringement under 35 U.S.C. § 271(e)(2)(A), intended to secure FDA approval to market a lower-cost generic alternative to PAZEO® prior to the expiration of the ’053 patent (Compl. ¶¶ 1, 34).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint alleges that Lupin's ANDA filing itself constitutes infringement and notes that Lupin's notice letter did not contest infringement of claims 1-6 and 8-12 of the ’053 patent (Compl. ¶ 32). The infringement theory is that the formulation described in Lupin's ANDA will, upon approval, meet all limitations of the asserted claims.

'053 Patent Infringement Allegations

Identified Points of Contention

• Technical Questions: The complaint's allegation that Lupin did not contest infringement in its notice letter suggests that the primary dispute may not be technical, but legal (Compl. ¶ 32). However, a central question for the court will be whether the specific formulation detailed in Lupin's confidential ANDA submission literally meets every limitation of the asserted claims, including the precise concentration ranges and excipient definitions.
• Scope Questions: The case will center on the statutory act of infringement under the Hatch-Waxman Act. The key question is whether the product that Lupin has asked the FDA for permission to sell is a product that is covered by the claims of the ’053 patent. Given the allegation that infringement was not contested in the notice letter, the dispute may shift almost entirely to Lupin's asserted defenses of invalidity or unenforceability (Compl. ¶ 30).

V. Key Claim Terms for Construction

The Term: "at least 0.67 w/v % olopatadine"

• Context and Importance: This term is the quantitative heart of the invention, defining the "high concentration" that distinguishes it from prior art. The infringement analysis will depend on whether Lupin's ANDA product meets this concentration floor. Practitioners may focus on this term because even minor deviations in concentration or measurement methodology could be argued to avoid infringement.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The plain language "at least" suggests a clear floor with no upper limit within the claim itself. The specification supports this by stating the formulation contains "at least 0.50%" and provides a series of increasing "more typically" values, with 0.67% being one of them ('053 Patent, col. 4:56-61).
  • Evidence for a Narrower Interpretation: The specification also provides an upper-end boundary, stating the concentration is "typically no greater than 1.0%" ('053 Patent, col. 4:60-61). A defendant could argue that the term should be understood within the context of the exemplified and preferred ranges, although this is less likely to succeed in limiting the clear "at least" language of the claim.

The Term: "a cyclodextrin selected from the group consisting of..."

• Context and Importance: This Markush group defines a critical solubilizing agent. The infringement analysis requires that the specific cyclodextrin in Lupin's product be one of the enumerated types. Practitioners may focus on this term because if Lupin's product uses a chemically distinct cyclodextrin, it could form a basis for a non-infringement argument.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The claim explicitly lists three alternative chemical structures. The specification describes them as serving the function of aiding "in solubilizing the olopatadine" ('053 Patent, col. 4:43-44).
  • Evidence for a Narrower Interpretation: The specification discusses the properties of these specific cyclodextrins in detail, including their potential to interfere with preservatives, suggesting their specific chemical nature is important ('053 Patent, col. 5:40-49). A defendant might argue that the term should be strictly limited to the exact chemical structures listed and not their equivalents.

VI. Other Allegations

• Indirect Infringement: The complaint alleges active inducement of infringement. This is based on the allegation that Lupin's proposed product labeling for its ANDA product will direct and encourage physicians and patients to administer the drug for the treatment of ocular allergic conjunctivitis, thereby causing infringing use (Compl. ¶¶ 37-38).
• Willful Infringement: The complaint alleges that Lupin acted with "full knowledge of the '053 patent" and that its submission of the ANDA was an act of infringement (Compl. ¶¶ 33, 41, 56). The basis for knowledge includes the patent's listing in the FDA's Orange Book and the statutory requirement for Lupin to send a notice letter to Alcon, which precipitated the lawsuit (Compl. ¶¶ 28, 29). The complaint seeks a declaration that the case is exceptional, which could entitle Alcon to attorneys' fees (Compl., Prayer for Relief (e)).

VII. Analyst’s Conclusion: Key Questions for the Case

• A core issue will be one of litigation strategy: given the complaint's allegation that Lupin did not contest infringement of numerous claims in its Paragraph IV notice letter, will infringement remain a central issue, or will the case pivot entirely to Lupin's affirmative defenses of patent invalidity and/or unenforceability?
• A key legal and factual question will be one of obviousness: assuming the case proceeds to the merits of validity, can Lupin demonstrate with clear and convincing evidence that a person of ordinary skill in the art would have been motivated to combine the specific claimed excipients (PEG, PVP, and a specific cyclodextrin) with a known drug (olopatadine) with a reasonable expectation of success in creating a stable, high-concentration ophthalmic formulation?
• A central question for damages and fees will be willfulness: did Lupin's challenge to the ’053 patent, as embodied in its Paragraph IV certification, lack a reasonable basis? The court's assessment of the strength of Lupin's invalidity arguments will be critical to determining whether its conduct was egregious enough to warrant enhanced damages or a finding that the case is exceptional.