Allergan v. Amneal Pharma LLC

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Allergan, Inc. (Delaware) and Saint Regis Mohawk Tribe (New York)
  • Defendant: Amneal Pharmaceuticals LLC (Delaware) and Amneal Pharmaceuticals Co. India Private Limited (India)
  • Plaintiff’s Counsel: Fish & Richardson P.C.; Drinker Biddle & Reath LLP
• Case Identification: 1:18-cv-01457, D. Del., 09/20/2018
• Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Amneal Pharmaceuticals LLC is a Delaware corporation, and Defendant Amneal Pharmaceuticals Co. India Private Limited is a foreign entity not resident in the United States.
• Core Dispute: Plaintiffs allege that Defendants' filing of an Abbreviated New Drug Application (ANDA) for a generic version of the dry eye treatment Restasis® constitutes an act of infringement of two patents covering specific formulations and methods of use for cyclosporine ophthalmic emulsions.
• Technical Context: The technology concerns low-concentration, oil-in-water ophthalmic emulsions of the immunosuppressant cyclosporine, used for increasing tear production in patients with chronic dry eye disease.
• Key Procedural History: The complaint notes that the patents-in-suit were previously asserted in the Eastern District of Texas against other generic manufacturers but were not litigated to a final judgment. In that prior case, four related patents were found invalid as obvious, a judgment that was pending appeal at the time of this complaint's filing. Subsequent to the filing of this complaint, Inter Partes Review (IPR) proceedings at the U.S. Patent and Trademark Office resulted in the cancellation of all claims of both patents-in-suit, U.S. Patent Nos. 8,633,162 and 8,642,556.

Case Timeline

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

U.S. Patent No. 8,633,162 - "Methods of Providing Therapeutic Effects Using Cyclosporin Components"

• Patent Identification: U.S. Patent No. 8,633,162, "Methods of Providing Therapeutic Effects Using Cyclosporin Components," issued January 21, 2014.

The Invention Explained

• Problem Addressed: The patent seeks to improve upon existing cyclosporine-containing emulsions for treating ophthalmic conditions. The background implies a need for formulations that maintain therapeutic efficacy while reducing potential side effects and drug interactions, thereby enhancing patient safety and prescribing flexibility (Compl. ¶1; ’162 Patent, col. 2:11-25).
• The Patented Solution: The invention is a method of treating dry eye disease using a specific oil-in-water emulsion. The solution involves using a therapeutically effective but low concentration of cyclosporin A (less than 0.1% by weight) combined with a hydrophobic component (such as castor oil) where the weight ratio of cyclosporin to the hydrophobic component is less than 0.8 ('162 Patent, Abstract, col. 2:29-36). This specific formulation is described as providing comparable efficacy to higher-concentration versions while offering advantages like reduced vision distortion and an improved safety profile ('162 Patent, col. 2:37-56).
• Technical Importance: The invention reflects an effort to optimize the delivery and formulation of a known active pharmaceutical ingredient to improve its clinical utility and patient tolerance for a chronic condition ('162 Patent, col. 2:15-25).

Key Claims at a Glance

• The complaint asserts the patent generally, with representative independent method claim 1 being central to the dispute.
• Essential elements of Independent Claim 1 include:
  • A method of treating dry eye disease.
  • Topically administering to the eye of a human in need thereof an emulsion at a frequency of twice a day.
  • The emulsion comprises cyclosporin A in an amount of about 0.05% by weight.
  • The emulsion comprises polysorbate 80, acrylate/C10-30 alkyl acrylate cross-polymer, water, and castor oil in an amount of about 1.25% by weight.
  • The emulsion is effective in treating dry eye disease.
• The complaint’s general allegations suggest a reservation of rights to assert any claims, including dependent ones.

U.S. Patent No. 8,642,556 - "Methods of Providing Therapeutic Effects Using Cyclosporin Components"

• Patent Identification: U.S. Patent No. 8,642,556, "Methods of Providing Therapeutic Effects Using Cyclosporin Components," issued February 4, 2014.

The Invention Explained

• Problem Addressed: As with the related ’162 Patent, the '556 Patent addresses the need for improved ophthalmic cyclosporine formulations that balance efficacy with safety and patient comfort ('556 Patent, col. 2:11-25).
• The Patented Solution: The '556 Patent claims a specific low-concentration (about 0.05%) cyclosporine emulsion that provides "overall efficacy substantially equal to" a higher-concentration (0.1%) formulation ('556 Patent, Claim 1). The invention is thus defined not just by its composition but also by its comparative therapeutic performance against a prior art benchmark, aiming to achieve the same result with a lower dose of the active ingredient ('556 Patent, col. 14:46-49).
• Technical Importance: The patent attempts to claim a specific "less is more" clinical outcome, where a lower-dose formulation is proven to be as effective as a higher-dose one, which can be a valuable differentiator in pharmaceutical development ('556 Patent, col. 2:15-25).

Key Claims at a Glance

• The complaint asserts the patent generally, with representative independent claim 1 being a key focus.
• Essential elements of Independent Claim 1 include:
  • A first topical ophthalmic emulsion for treating an eye of a human.
  • The emulsion comprises cyclosporin A (about 0.05%), polysorbate 80, an acrylate cross-polymer, water, and castor oil (about 1.25%).
  • The emulsion is therapeutically effective.
  • The emulsion provides "overall efficacy substantially equal to a second topical ophthalmic emulsion" containing about 0.1% cyclosporin A.
• The complaint’s general allegations suggest a reservation of rights to assert any claims, including dependent ones.

III. The Accused Instrumentality

• Product Identification: The accused instrumentality is Defendants' "Cyclosporine Ophthalmic Emulsion, 0.05%," which is the subject of Abbreviated New Drug Application (ANDA) No. 211909 submitted to the FDA (Compl. ¶12).
• Functionality and Market Context: The product is a generic version of Allergan’s RESTASIS® and is intended to be used for the same therapeutic purpose: treating chronic dry eye (Compl. ¶¶1, 12). The complaint alleges that the product described in the ANDA contains the same active ingredient at the same concentration as specified in the asserted patents (Compl. ¶12). Plaintiffs allege that Defendants' product, if approved, will be sold nationwide and will directly compete with and displace sales of RESTASIS® (Compl. ¶¶14, 15).
• No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint alleges that the submission of ANDA No. 211909 is a technical act of infringement under 35 U.S.C. § 271(e)(2)(A), as the product described therein, if commercially manufactured and sold, would infringe the patents-in-suit (Compl. ¶¶44, 70).

’162 Patent Infringement Allegations

’556 Patent Infringement Allegations

• Identified Points of Contention:
  • Scope Questions: A central question would be the proper construction of "about" as it applies to the weight percentages of cyclosporin A and castor oil. The parties would likely dispute how much variation from the specified "0.05%" and "1.25%" is permissible under this term.
  • Technical Questions: For the ’556 Patent, a key dispute would concern the meaning of "provides overall efficacy substantially equal to" the 0.1% formulation. The question is whether meeting the FDA’s regulatory standard for bioequivalence is sufficient to satisfy this claim limitation, or if the patent requires a different, perhaps more stringent, evidentiary showing of equivalence.

V. Key Claim Terms for Construction

• The Term: "about" (e.g., "about 0.05% by weight")

  • Context and Importance: This term's construction is critical for determining the literal scope of the claimed formulation. A narrow interpretation could provide a path for non-infringement, while a broader one would capture more formulations. Practitioners may focus on this term because infringement in a pharmaceutical case often turns on slight variations in formulation.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent specification uses the term "therapeutically effective amount of less than 0.1% by weight," suggesting the claims are not strictly limited to a single value but encompass a range below 0.1% ('162 Patent, Abstract).
    • Evidence for a Narrower Interpretation: The patent’s Example 1 and its corresponding tables describe "Composition II" as containing exactly "0.05" wt % Cyclosporin A, which could be used to argue that "about 0.05%" should be interpreted very narrowly around that specific value ('162 Patent, col. 13-14).

• The Term: "provides overall efficacy substantially equal to"

  • Context and Importance: This functional limitation is the core distinguishing feature of claim 1 of the ’556 Patent. Its definition is dispositive for infringement, as it requires a comparison between the accused product and a hypothetical 0.1% formulation.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: A plaintiff may argue this term simply means the formulation meets the FDA standard for bioequivalence, a showing the defendant must make in its ANDA to gain approval for a generic drug.
    • Evidence for a Narrower Interpretation: The specification explicitly states that "Composition II" (the 0.05% formulation) "provides overall efficacy in treating dry eye disease substantially equal to that of Composition I" (the 0.1% formulation) based on the results of a "Phase 3, double-masked, randomized, parallel group study" ('556 Patent, col. 14:40-49). A defendant could argue this language tethers the meaning of "substantially equal" to the specific outcome of that clinical trial, requiring more than a simple bioequivalence showing.

VI. Other Allegations

• Indirect Infringement: The complaint alleges both induced and contributory infringement for both patents. The inducement theory is based on the allegation that Amneal’s product labeling will instruct physicians and patients to administer the drug in a manner that directly infringes the claimed methods (Compl. ¶¶ 46, 55-59, 73, 91-95). The contributory infringement theory is based on the allegation that Amneal's product is especially made for infringing the method claims and is not a staple article of commerce with substantial non-infringing uses (Compl. ¶¶ 47, 60-63, 74, 96-99).
• Willful Infringement: The complaint alleges that Amneal had knowledge of the patents-in-suit no later than the date they were listed in the FDA's Orange Book and proceeded with its ANDA filing despite this knowledge, constituting willful, wanton, and deliberate conduct (Compl. ¶¶ 68, 104).

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

While the complaint outlines a standard Hatch-Waxman dispute over claim scope and infringement, subsequent procedural developments have fundamentally altered the landscape of this case. The central questions are now procedural and existential rather than technical.

• A primary question is one of jurisdiction and mootness: given that the U.S. Patent and Trademark Office issued IPR certificates in 2021 cancelling all asserted claims of both patents-in-suit, the foundational basis for the infringement action appears to have been eliminated. A court would need to determine if any viable controversy remains that would prevent dismissal of the case.
• A second, related question is the legal effect of the IPR cancellations: the cancellation of all claims ab initio raises the issue of whether Plaintiffs have any assertable patent rights for the entire period of the lawsuit. This procedural history overshadows any technical debate over infringement or claim construction that was at issue when the complaint was filed.