Alcon Research Ltd v. Cipla Ltd

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Alcon Research, Ltd. (Delaware)
  • Defendant: Cipla Limited (India) and Cipla USA, Inc. (Delaware)
  • Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP; Williams & Connolly LLP
• Case Identification: Alcon Research Ltd v. Cipla Ltd, 1:17-cv-01244, D. Del., 08/31/2017
• Venue Allegations: Venue is alleged to be proper in Delaware as Defendant Cipla USA, Inc. is a Delaware corporation, and its parent, Cipla Ltd., is alleged to have purposefully availed itself of Delaware's laws through its subsidiary and to regularly engage in patent litigation in the district.
• Core Dispute: Plaintiff alleges that Defendants’ filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's PAZEO® ophthalmic solution constitutes an act of infringement of two patents covering high-concentration olopatadine formulations.
• Technical Context: The technology involves aqueous ophthalmic solutions containing a high concentration of the antihistamine olopatadine, stabilized with specific excipients, for the once-daily treatment of ocular allergic conjunctivitis.
• Key Procedural History: The lawsuit was initiated under the Hatch-Waxman Act following a notice letter from Cipla, dated July 19, 2017, informing Alcon of its ANDA filing. The notice included a Paragraph IV certification, asserting that Alcon's patents are invalid, unenforceable, and/or will not be infringed by the proposed generic product.

Case Timeline

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

U.S. Patent No. 8,791,154 - "High Concentration Olopatadine Ophthalmic Composition"

• Issued: July 29, 2014

The Invention Explained

• Problem Addressed: The patent describes the technical challenge of creating a stable, topically administered ophthalmic solution with a high concentration of the active ingredient olopatadine. (’154 Patent, col. 2:1-6). Olopatadine's limited solubility in water makes it difficult to formulate at concentrations high enough to effectively treat the late-phase symptoms of allergic conjunctivitis, which existing commercial products were not believed to fully address. (’154 Patent, col. 1:25-39).
• The Patented Solution: The invention is an aqueous formulation that achieves a high concentration of olopatadine (at least 0.67 w/v%) by using a specific combination of solubilizing agents. The key components include a cyclodextrin derivative (e.g., hydroxypropyl-γ-cyclodextrin), a lactam polymer (e.g., polyvinylpyrrolidone or PVP), and a polyether (e.g., polyethylene glycol or PEG), which work together to dissolve and stabilize the drug. (’154 Patent, Abstract; col. 2:41-58).
• Technical Importance: This formulation enabled the development of a once-daily eye drop capable of providing enhanced, full-day relief from both early- and late-phase allergy symptoms, including a significant reduction in ocular redness. (’154 Patent, col. 1:42-56).

Key Claims at a Glance

• The complaint asserts independent claims 1, 4, 12, and 21 (Compl. ¶31). The essential elements of independent composition claim 1 are:
  • 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 300 to 500;
  • polyvinylpyrrolidone;
  • hydroxypropyl-γ-cyclodextrin;
  • benzalkonium chloride; and
  • water.
• The complaint reserves the right to assert additional claims.

U.S. Patent No. 9,533,053 - "High Concentration Olopatadine Ophthalmic Composition"

• Issued: January 3, 2017

The Invention Explained

• Problem Addressed: As a continuation of the application leading to the ’154 Patent, this patent addresses the same problem: the difficulty of creating a stable, high-concentration aqueous solution of olopatadine for treating ocular allergies. (’053 Patent, col. 2:4-9).
• The Patented Solution: The invention claims ophthalmic compositions that use a cyclodextrin derivative, along with other excipients like PEG and PVP, to solubilize a high concentration of olopatadine (at least 0.67 w/v%). (’053 Patent, Abstract; col. 2:47-61). The claimed combinations allow the formulation to remain stable and achieve desired pharmaceutical properties for topical eye delivery.
• Technical Importance: The technology provides a formulation for a once-a-day treatment for allergic conjunctivitis that offers improved efficacy against a broader range of symptoms, particularly those associated with the late-phase allergic response. (’053 Patent, col. 1:45-58).

Key Claims at a Glance

• The complaint asserts at least independent claims 1 and 8 (Compl. ¶53). The essential elements of independent composition claim 1 are:
  • 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 SAE-β-cyclodextrin, hydroxypropyl-β-cyclodextrin, and hydroxypropyl-γ-cyclodextrin; and
  • water.
• The complaint reserves the right to assert additional claims.

III. The Accused Instrumentality

• Product Identification: "Cipla's ANDA Product," identified as a generic version of PAZEO® ophthalmic solution, associated with ANDA No. 210336 (Compl. ¶¶1-2).
• Functionality and Market Context: The complaint alleges, upon information and belief, that the accused ANDA product is a drug product containing the "same or equivalent ingredients in the same or equivalent amounts" as PAZEO® (Compl. ¶2). PAZEO® is Alcon's commercial product for treating ocular allergic conjunctivitis and is listed in the FDA's Orange Book as being covered by the patents-in-suit (Compl. ¶¶28, 50). The infringement alleged is the statutory act of filing the ANDA to obtain FDA approval for commercial manufacture and sale of this generic product prior to the expiration of the asserted patents (Compl. ¶1, ¶34, ¶56). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint alleges that because the accused ANDA product is a generic version of PAZEO®, it necessarily contains the same ingredients and thus infringes the claims covering the PAZEO® formulation (Compl. ¶¶2, 31, 53).

8,791,154 Infringement Allegations

9,533,053 Infringement Allegations

• Identified Points of Contention:
  • Factual Question: The primary factual question for infringement is whether Cipla's ANDA formulation is, in fact, bioequivalent and compositionally identical to a formulation covered by the asserted claims. The complaint's allegation that the products are the "same or equivalent" (Compl. ¶2) raises the question of whether "equivalent" is sufficient for literal infringement, which requires every claim limitation to be met exactly.
  • Scope Question: The complaint notes that in its notice letter, Cipla did not contest infringement of numerous claims (including claims 1-6 of the ’154 and ’053 patents) on any basis other than invalidity (Compl. ¶32, ¶54). This suggests that for these claims, the dispute may center entirely on validity, with the infringement analysis itself being a secondary issue or potentially stipulated.

V. Key Claim Terms for Construction

• The Term: "at least 0.67 w/v % olopatadine" (’154 Patent, Claim 1; ’053 Patent, Claim 1)
• Context and Importance: This term defines the "high concentration" threshold that is central to the patents' assertion of novelty and improved efficacy for late-phase symptoms. Its construction is critical because it sets the lower boundary for both infringement and obviousness analyses. Practitioners may focus on this term because the patents tie statistically significant improvements in efficacy to concentrations "of about 0.7 w/v % olopatadine and above" (’154 Patent, col. 3:65-67).
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The use of "at least" suggests a floor, not a ceiling, giving the term a clear and broad scope covering any concentration at or above the specified value. The specification consistently frames 0.7% as the point where enhanced efficacy "begins to show statistically significant improvements" (’154 Patent, col. 3:64-66), supporting the idea that the invention covers this level and higher.
  • Evidence for a Narrower Interpretation: A party could argue that the term should be limited by the specific examples, though the claims themselves are not explicitly so limited. More likely, any dispute would concern the precision of "0.67 w/v %" and whether standard pharmaceutical measurement tolerances could place an allegedly infringing product just outside this literal scope.

VI. Other Allegations

• Indirect Infringement: The complaint alleges active inducement, asserting that Cipla's proposed product labeling will instruct physicians and patients to administer the ANDA product in a manner that infringes Alcon's method claims (Compl. ¶38, ¶60). It also pleads contributory infringement, alleging the ANDA product is especially adapted for an infringing use and is not a staple article of commerce (Compl. ¶39, ¶76).
• Willful Infringement: Willfulness is alleged based on Cipla's pre-suit knowledge of the patents, as evidenced by its July 19, 2017 notice letter and Paragraph IV certification (Compl. ¶33, ¶55). The complaint asserts Cipla acted "without a reasonable basis for believing that it would not be liable for infringement" (Compl. ¶42, ¶63).

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

As is common in ANDA litigation, the central conflict suggested by the complaint is not over whether the proposed generic copies the patented product, but whether the patent covering that product is valid. The key questions for the court will likely be:

1. A central issue will be one of validity, specifically obviousness: given the known problem of olopatadine's poor solubility, was it obvious to a person of ordinary skill in pharmaceutical formulation to combine a high concentration of the drug (≥0.67 w/v%) with the claimed multi-part system of excipients (i.e., a cyclodextrin, PVP, and PEG) with a reasonable expectation of success in creating a stable, once-daily ophthalmic solution?

2. A key evidentiary question will be one of compositional identity: will discovery confirm the complaint's allegation that Cipla’s proposed ANDA product formulation meets every quantitative and qualitative limitation of at least one asserted claim, or are there subtle but material differences in ingredients or concentrations that could support a non-infringement argument?

3. A secondary issue may be one of claim scope: how will the court construe the numerical ranges and Markush groups in the claims? The resolution of these terms will define the field of play for both the infringement analysis and the evaluation of prior art for the obviousness determination.