Bausch Health Ireland Ltd v. Mylan Pharma Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Bausch Health Ireland Limited (Ireland) and Salix Pharmaceuticals, Inc. (California)
  • Defendant: Mylan Pharmaceuticals Inc. (Delaware)
  • Plaintiff’s Counsel: Thomas Combs & Spann, PLLC
• Case Identification: 1:24-cv-00036, N.D. W. Va., 04/05/2024
• Venue Allegations: Plaintiffs allege venue is proper because Defendant Mylan Pharmaceuticals Inc. has a place of business in Morgantown, West Virginia, conducts business in the district, has previously submitted to the court's jurisdiction, and its Abbreviated New Drug Application (ANDA) filing indicates a plan to market its generic drug in the district.
• Core Dispute: Plaintiffs allege that Defendant’s filing of an ANDA to market a generic version of the drug Trulance® constitutes an act of infringement of a patent covering purified oral formulations of the active ingredient, plecanatide.
• Technical Context: The technology relates to pharmaceutical compositions of plecanatide, a peptide agonist used to treat gastrointestinal disorders such as chronic idiopathic constipation and irritable bowel syndrome.
• Key Procedural History: This is a Hatch-Waxman action triggered by Defendant’s filing of ANDA No. 215686 with a Paragraph IV certification, challenging U.S. Patent No. 11,834,521, which is listed in the FDA's Orange Book for Trulance®. Plaintiffs state they received Defendant's notice letter on March 6, 2024.

Case Timeline

Date	Event
2013-06-05	’521 Patent Priority Date
2017-01-19	FDA Approval of Trulance® (NDA No. 208745)
2023-12-05	’521 Patent Issue Date
2024-03-06	Plaintiffs Receive Defendant's ANDA Notice Letter
2024-04-05	Complaint Filing Date

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

U.S. Patent No. 11,834,521 - "Ultra-Pure Agonists of Guanylate Cyclase C, Method of Making and Using Same"

• Patent Identification: U.S. Patent No. 11,834,521 (“’521 Patent”), issued December 5, 2023.

The Invention Explained

• Problem Addressed: The patent describes challenges in synthesizing peptides like plecanatide for pharmaceutical use, noting that previous methods resulted in low yields or high levels of impurities ('521 Patent, col. 3:33-44). Specifically, it identifies that prior lyophilization processes could enrich for acetamide impurities, while precipitation processes could lead to high levels of residual solvents and the formation of thermal degradants, compromising the product's stability and shelf life ('521 Patent, col. 8:1-34).
• The Patented Solution: The invention claims to solve these issues through improved purification processes that yield a highly pure and stable peptide ('521 Patent, Abstract). The patent focuses on the final composition, claiming an oral formulation containing a purified peptide defined by specific physical and chemical characteristics, such as low bulk density and strictly controlled low levels of specific impurities, including a thermal degradant and topoisomers ('521 Patent, col. 8:52-61; col. 186:12-25).
• Technical Importance: The claimed solution provides a form of the plecanatide drug substance with characteristics suitable for large-scale pharmaceutical manufacturing and a stable final drug product, addressing key quality control and safety issues in drug development ('521 Patent, col. 8:35-43).

Key Claims at a Glance

• The complaint asserts infringement of at least one claim of the '521 patent (Compl. ¶22). The first independent claim, Claim 1, is representative of the invention's composition claims.
• Claim 1 of the '521 Patent recites:
  • An oral formulation comprising a purified peptide comprising the Guanylate Cyclase-C(GCC) agonist of amino acid sequence of SEQ ID NO: 1,
  • characterized in that the purified peptide has:
  • a) a bulk density of not greater than 0.1 g/mL;
  • b) less than 0.25% alpha-Asp-9-plecanatide relative to the weight of the purified peptide; and
  • c) less than 2% by weight of topoisomers relative to the weight of the purified peptide.
• The complaint does not explicitly reserve the right to assert dependent claims but makes a general allegation against the patent.

III. The Accused Instrumentality

Product Identification

• Defendant’s proposed generic plecanatide oral tablets, 3 mg, which are the subject of ANDA No. 215686 submitted to the FDA (Compl. ¶4, 13).

Functionality and Market Context

• The accused product is intended to be a generic version of Plaintiffs’ commercial product, Trulance® (Compl. ¶14, 17).
• The complaint alleges that as part of the ANDA process, Defendant's product must be bioequivalent to Trulance® and is therefore "the same, or substantially the same" as Plaintiffs' product (Compl. ¶18, 20). The product is designed for oral administration to treat gastrointestinal disorders.

IV. Analysis of Infringement Allegations

The complaint does not provide specific technical allegations mapping elements of the accused product to the patent claims. The infringement theory is based on the statutory framework of the Hatch-Waxman Act, where the filing of the ANDA itself is the act of infringement under 35 U.S.C. § 271(e)(2) (Compl. ¶22). The central allegation is that because Defendant's product is intended as a generic equivalent to Trulance®, it will, upon approval and marketing, necessarily meet the limitations of at least one claim of the ’521 Patent (Compl. ¶23). The complaint notes that Defendant's Paragraph IV notice letter provided "no explanation of any non-infringement defense" (Compl. ¶19).

No probative visual evidence provided in complaint.

• Identified Points of Contention:
  • Scope Questions: The dispute may center on whether the proposed generic product falls within the specific quantitative limits of the claims. For example, does Defendant's product, as formulated, possess a "bulk density of not greater than 0.1 g/mL" and contain "less than 0.25% alpha-Asp-9-plecanatide" and "less than 2% by weight of topoisomers"?
  • Technical Questions: A primary technical question, answerable only through discovery of the confidential ANDA, is what are the actual measured characteristics of Defendant's proposed product? The case will likely involve detailed analytical testing to determine if the generic formulation meets the specific purity and physical property limitations recited in the asserted claims.

V. Key Claim Terms for Construction

• The Term: "bulk density"

• Context and Importance: This quantitative physical parameter is a key limitation of the claimed purified peptide. Infringement will depend directly on whether the measured bulk density of Defendant's product is "not greater than 0.1 g/mL." Practitioners may focus on this term because the specific methodology for measuring bulk density could be a point of dispute, and different methods could yield results that fall on either side of the claimed threshold.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The patent does not appear to provide a special definition for "bulk density," suggesting that its plain and ordinary meaning in the context of pharmaceutical powders would apply.
  • Evidence for a Narrower Interpretation: The specification provides an example of a lyophilized product having a bulk density of 0.0332 g/mL, which meets the claim limitation, and contrasts it with a precipitated product having a much higher density of 0.486 g/mL ('521 Patent, col. 8:53-54; Table XVIII). A party could argue that the term should be interpreted in light of the methods and examples disclosed in the patent.

• The Term: "alpha-Asp-9-plecanatide"

• Context and Importance: This term identifies a specific impurity that must be present at a level "less than 0.25%." This negative limitation is critical, as infringement hinges on demonstrating that the accused product contains this impurity below the specified threshold.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The term is a specific chemical name, which has a clear and unambiguous meaning to a person of ordinary skill in the art.
  • Evidence for a Narrower Interpretation: The patent provides significant context, identifying it as a "thermal degradant" having a "Relative Retention Time (RRT) of ~1.33 from ultra-performance liquid chromatography (UPLC) analysis" ('521 Patent, col. 8:20-24). This provides a specific analytical signature that could be used to define the term's scope within the context of the patent.

VI. Other Allegations

• Indirect Infringement: The complaint includes claims for contributory and induced infringement "upon information and belief" (Compl. ¶24). The basis for these allegations is that Defendant's future commercial activities, including the marketing and sale of its generic product with an instructional label, will cause and encourage infringement by others, such as patients and healthcare providers.
• Willful Infringement: The complaint does not contain an explicit count for willful infringement. However, the prayer for relief requests a declaration that the case is "exceptional under 35 U.S.C. §§ 285" (Prayer for Relief ¶5). Such a declaration, which can lead to an award of attorney's fees, is often predicated on findings of willful infringement or litigation misconduct. The basis for knowledge is Defendant's Paragraph IV certification against a patent listed in the FDA's Orange Book (Compl. ¶11, 15).

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

The resolution of this ANDA litigation will likely depend on the answers to two central questions that can only be resolved after discovery into the contents of Defendant's confidential FDA submission.

• A key evidentiary question will be one of product characterization: Does Mylan's proposed generic plecanatide formulation, as produced by its manufacturing process, actually possess the specific physical and chemical properties required by the asserted claims, particularly the low bulk density and the specified low levels of alpha-Asp-9-plecanatide and topoisomers?
• A core issue will be one of analytical proof: Given the claim's quantitative limitations, the case may turn on the selection and execution of testing methodologies. Can Plaintiffs prove, by a preponderance of the evidence, that the accused product meets every limitation, and what analytical methods will the court deem appropriate for measuring "bulk density" and the percentage of specific impurities?