Allergan Inc v. TWi Pharma Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Allergan, Inc. (Delaware)
  • Defendant: TWi Pharmaceuticals, Inc. (Taiwan) and TWi Pharmaceuticals USA, Inc. (Delaware)
  • Plaintiff’s Counsel: Fish & Richardson P.C.
• Case Identification: 1:16-cv-00620, D. Del., 07/20/2016
• Venue Allegations: Venue is based on Defendant TWi-USA being a Delaware corporation with a registered agent in the state. The complaint further alleges that Defendants intend to distribute and sell the accused product in Delaware, thereby causing injury to Plaintiff in the district.
• Core Dispute: Plaintiff alleges that Defendants’ submission of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff’s Restasis® product constitutes an act of infringement of six patents directed to ophthalmic emulsions containing cyclosporine.
• Technical Context: The technology concerns pharmaceutical formulations for treating chronic dry eye disease, a common ophthalmic condition, by administering an oil-in-water emulsion containing the immunosuppressant cyclosporine.
• Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants’ submission of ANDA No. 209064 to the U.S. Food and Drug Administration (FDA). The ANDA included a Paragraph IV certification, notice of which was received by Plaintiff on or about June 10, 2016, alleging that Plaintiff's Orange Book-listed patents for Restasis® are invalid, unenforceable, or will not be infringed by the proposed generic product.

Case Timeline

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

U.S. Patent No. 8,629,111 - "Methods of Providing Therapeutic Effects Using Cyclosporin Components"

• Patent Identification: U.S. Patent No. 8,629,111, titled “Methods of Providing Therapeutic Effects Using Cyclosporin Components,” issued January 14, 2014 (Compl. ¶18).

The Invention Explained

• Problem Addressed: The patent background identifies a continuing need for "enhanced methods of treating ophthalmic or ocular conditions with cyclosporin-containing emulsions" (Compl. Ex. 1, ’111 Patent, col. 1:53-56).
• The Patented Solution: The invention provides ophthalmic emulsions with a therapeutically effective amount of cyclosporine that is less than 0.1% by weight. The patent teaches that using a relatively low concentration of the active ingredient, in combination with a specific and relatively high concentration of a hydrophobic component like castor oil, provides comparable therapeutic efficacy to higher-dose formulations while enhancing patient safety and prescribing flexibility (’111 Patent, Abstract; col. 2:15-27, 40-51).
• Technical Importance: This approach sought to improve the clinical profile of topical cyclosporine treatment by achieving therapeutic benefits with a lower drug concentration, thereby mitigating potential side effects and drug interactions associated with the active ingredient (’111 Patent, col. 2:18-24).

Key Claims at a Glance

• The complaint does not identify specific claims but makes a general allegation of infringement (Compl. ¶56). Independent claim 1 is representative of the patented composition:
• A topical ophthalmic emulsion for treating an eye of a human comprising:
  • cyclosporin A in an amount of about 0.05% by weight,
  • polysorbate 80,
  • acrylate/C10-30 alkyl acrylate cross-polymer,
  • water, and
  • castor oil in an amount of about 1.25% by weight;
  • wherein cyclosporin A is the only peptide present in the topical ophthalmic emulsion.

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

• Patent Identification: U.S. Patent No. 8,633,162, titled “Methods of Providing Therapeutic Effects Using Cyclosporin Components,” issued January 21, 2014 (Compl. ¶23).

The Invention Explained

• Problem Addressed: The patent addresses the need for improved methods of treating ophthalmic conditions, particularly dry eye disease, using cyclosporine formulations (Compl. Ex. 2, ’162 Patent, col. 1:53-56).
• The Patented Solution: The invention is a method of treating dry eye disease by administering a specific low-concentration cyclosporine emulsion. Like the ’111 Patent, the method relies on an emulsion with less than 0.1% cyclosporine and a weight ratio of the cyclosporine component to the hydrophobic component of less than 0.08, which is described as providing substantial efficacy with an improved safety profile (’162 Patent, Abstract; col. 2:15-27).
• Technical Importance: The invention provided a method of using a low-dose formulation to achieve therapeutic efficacy comparable to higher-dose versions, thereby offering physicians a treatment option with potentially fewer side effects and greater flexibility (’162 Patent, col. 2:18-24).

Key Claims at a Glance

• The complaint does not identify specific claims asserted against the accused product (Compl. ¶93). Independent claim 1 is representative of the patented method:
• A method of treating dry eye disease, the method comprising:
  • topically administering to the eye of a human in need thereof an emulsion at a frequency of twice a day,
  • wherein the emulsion comprises cyclosporin A in an amount of about 0.05% by weight, polysorbate 80, acrylate/C10-30 alkyl acrylate cross-polymer, water, and castor oil in an amount of about 1.25% by weight; and
  • wherein the topical ophthalmic emulsion is effective in treating dry eye disease.

Multi-Patent Capsule: U.S. Patent No. 8,642,556

• Patent Identification: U.S. Patent No. 8,642,556, titled “Methods of Providing Therapeutic Effects Using Cyclosporin Components,” issued February 4, 2014 (Compl. ¶28).
• Technology Synopsis: The patent claims a topical ophthalmic emulsion containing about 0.05% cyclosporin A and about 1.25% castor oil. The claims describe the formulation as providing efficacy substantially equal to a higher-concentration (0.1%) cyclosporin emulsion, thereby achieving a therapeutic benefit with a lower dose of the active ingredient (Compl. Ex. 3, ’556 Patent, Claim 1).
• Asserted Claims: The complaint does not identify specific asserted claims (Compl. ¶¶120-121). Independent claims 1 and 13 are directed to the ophthalmic emulsion.
• Accused Features: The accused instrumentality is Defendants' proposed generic 0.05% cyclosporine ophthalmic emulsion (Compl. ¶¶117-118).

Multi-Patent Capsule: U.S. Patent No. 8,648,048

• Patent Identification: U.S. Patent No. 8,648,048, titled “Methods of Providing Therapeutic Effects Using Cyclosporin Components,” issued February 11, 2014 (Compl. ¶33).
• Technology Synopsis: The patent claims methods of increasing tear production by administering the specified low-dose cyclosporine emulsion. The invention is based on the use of a formulation with about 0.05% cyclosporin A and about 1.25% castor oil to treat conditions like keratoconjunctivitis sicca (Compl. Ex. 4, ’048 Patent, Claims 1, 18, 22).
• Asserted Claims: The complaint does not identify specific asserted claims (Compl. ¶¶155-156). Independent claims 1, 13, 18, and 22 are directed to methods of treatment.
• Accused Features: The accused instrumentality is the proposed generic drug and the method of its administration for FDA-approved indications (Compl. ¶¶153, 155-156).

Multi-Patent Capsule: U.S. Patent No. 8,685,930

• Patent Identification: U.S. Patent No. 8,685,930, titled “Methods of Providing Therapeutic Effects Using Cyclosporin Components,” issued April 1, 2014 (Compl. ¶38).
• Technology Synopsis: The patent claims topical ophthalmic emulsions and methods of treating keratoconjunctivitis sicca using the low-dose cyclosporine formulation. The claims recite the specific formulation containing about 0.05% cyclosporin A and about 1.25% castor oil, among other excipients (Compl. Ex. 5, ’930 Patent, Claims 1, 13, 25).
• Asserted Claims: The complaint does not identify specific asserted claims (Compl. ¶¶182-183). Independent claims 1, 13, and 25 are directed to compositions and methods.
• Accused Features: The accused instrumentality is Defendants' proposed generic 0.05% cyclosporine ophthalmic emulsion and its intended use (Compl. ¶¶179, 182-183).

Multi-Patent Capsule: U.S. Patent No. 9,248,191

• Patent Identification: U.S. Patent No. 9,248,191, titled “Methods of Providing Therapeutic Effects Using Cyclosporin Components,” issued February 2, 2016 (Compl. ¶43).
• Technology Synopsis: This patent is part of the same family and covers methods of treatment using the same low-dose cyclosporine emulsion technology as the other patents-in-suit. The invention focuses on achieving therapeutic efficacy with a favorable safety profile (Compl. ¶¶43, 215, 217-218).
• Asserted Claims: The complaint does not identify specific asserted claims (Compl. ¶¶217-218).
• Accused Features: The accused instrumentality is Defendants' proposed generic 0.05% cyclosporine ophthalmic emulsion and its intended method of use (Compl. ¶215).

III. The Accused Instrumentality

Product Identification

• The accused instrumentality is Defendants' "Cyclosporine Ophthalmic Emulsion, 0.05%," which is the subject of ANDA No. 209064 submitted to the FDA (Compl. ¶48).

Functionality and Market Context

• The complaint describes the product as a "generic version of Allergan's RESTASIS® product" (Compl. ¶48). Its function is to provide a topical treatment for ophthalmic conditions, such as chronic dry eye. The complaint alleges that upon receiving FDA approval, Defendants intend to engage in the commercial manufacture, marketing, and sale of this product in the United States, which would directly compete with and displace sales of Plaintiff's branded Restasis® product (Compl. ¶¶16, 52-53). The complaint does not provide further technical details regarding the specific formulation of the accused product beyond its active ingredient and concentration. No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not contain a claim chart or provide a detailed mapping of the accused product to any specific claim elements. The analysis below is based on the composition recited in representative independent claim 1 of the ’111 Patent and the method recited in representative independent claim 1 of the ’162 Patent.

8,629,111 Patent Infringement Allegations

8,633,162 Patent Infringement Allegations

Identified Points of Contention

• Scope Questions: A central issue for claim construction may be the interpretation of the term "about" as it applies to the weight percentages of cyclosporin A ("about 0.05%") and castor oil ("about 1.25%"). The permissible range of deviation from these figures will be critical to the infringement analysis.
• Technical Questions: As the complaint does not detail the excipients in the accused formulation, a key factual question will be whether the product described in ANDA No. 209064 actually contains each of the specifically claimed components (polysorbate 80, the specified acrylate cross-polymer, castor oil) in the claimed amounts. The case will likely depend on discovery into the contents of the ANDA. For the method claims, a question will be whether the proposed product label will instruct administration in a manner that meets all steps of the claimed method.

V. Key Claim Terms for Construction

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

• Context and Importance: This term appears in the quantification of the active ingredient and key excipients in the independent claims of multiple patents-in-suit. The scope of this term is central to the dispute, as even a small deviation in the concentration of these components in the accused product could form the basis of a non-infringement argument. Practitioners may focus on this term because infringement will hinge on whether the concentrations in the ANDA product fall within the range encompassed by "about."
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The specification does not provide an explicit definition for "about," which could support an interpretation consistent with its ordinary meaning of "approximately" or encompassing normal manufacturing tolerances (’111 Patent, col. 10:22-30).
  • Evidence for a Narrower Interpretation: The patent's Example 1 provides a specific formulation ("Composition II") with precise values of 0.05% cyclosporin and 1.25% castor oil (’111 Patent, col. 10:22-30). A party could argue that this example limits the scope of "about" to a very narrow range around the stated values.

The Term: "effective in treating dry eye disease" (’162 Patent, Claim 1)

• Context and Importance: This functional language in the preamble and body of method claims requires that the administered emulsion achieves a specific therapeutic result. A defendant might challenge this term as indefinite or argue that its product, while approved for the same indication, is not "effective" in the manner contemplated by the patent, potentially creating a non-infringement defense.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The detailed description broadly discusses the utility of cyclosporine components in treating dry eye syndrome and related conditions, suggesting "effective" could be construed to mean providing any measurable clinical benefit for the condition (’162 Patent, col. 4:55-67).
  • Evidence for a Narrower Interpretation: The specification discusses a clinical study where the claimed 0.05% emulsion was found to provide "overall efficacy in treating dry eye disease substantially equal to that of" a 0.1% formulation (’162 Patent, col. 10:35-41). A party could argue this passage defines "effective" as achieving a level of efficacy comparable to that of the higher-concentration product.

VI. Other Allegations

• Indirect Infringement: The complaint alleges both induced and contributory infringement for all six patents-in-suit. The inducement allegations are based on Defendants' knowledge that the commercial sale of their product will cause infringement by end-users (patients) and medical professionals who follow the product's instructions for use (Compl. ¶¶58, 93). Contributory infringement is alleged on the basis that the accused product is especially made or adapted for an infringing use and is not a staple article of commerce with substantial non-infringing uses (Compl. ¶¶59, 94).
• Willful Infringement: For several patents, the complaint alleges that Defendants acted willfully despite having actual notice of the patents, at least from the date they were listed in the FDA's Orange Book (Compl. ¶¶89, 115). This allegation forms the basis for seeking enhanced damages and attorneys' fees.

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

• A central evidentiary question will be one of compositional identity: does the generic formulation described in Defendants’ confidential ANDA contain the exact excipients (polysorbate 80, a specific acrylate/C10-30 alkyl acrylate cross-polymer, and castor oil) in amounts that fall within the scope of the claims, particularly as defined by the term "about"?
• The case will also involve a core issue of infringement methodology: for the asserted method claims, does the proposed product labeling for the generic drug instruct administration in a manner that meets every limitation of the claimed methods, thereby supporting Plaintiff's claims of induced infringement?
• Finally, a key legal question will be one of claim scope: how will the court construe the functional limitation "effective in treating dry eye disease," and what level of clinical evidence will be required to prove that the accused method satisfies this requirement?