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: 1:22-cv-00085, N.D. W. Va., 09/01/2022
• Venue Allegations: Plaintiffs allege venue is proper in the Northern District of West Virginia because Mylan Pharmaceuticals Inc. maintains a place of business in the district, is registered to do business there, has previously submitted to the court's jurisdiction, and the district is a likely destination for sales of the accused generic product upon FDA approval.
• Core Dispute: Plaintiffs allege that Defendant's filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Trulance® (plecanatide) constitutes an act of infringement of two patents covering highly purified oral formulations of the peptide.
• Technical Context: The technology concerns methods for purifying the peptide plecanatide—a guanylate cyclase-C agonist for treating gastrointestinal disorders—to achieve specific purity and physical characteristics suitable for a stable and effective oral drug formulation.
• Key Procedural History: This is a Hatch-Waxman lawsuit initiated in response to Defendant Mylan’s submission of ANDA No. 215686 with a Paragraph IV certification, challenging patents listed in the FDA’s Orange Book for Plaintiffs’ branded drug, Trulance®. The action was triggered by Plaintiffs’ receipt of Mylan's notice letter regarding the ANDA filing.

Case Timeline

Date	Event
2013-06-05	Earliest Priority Date for ’549 & ’346 Patents
2017-01-19	FDA Approval of Trulance® (NDA No. 208745)
2021-10-12	U.S. Patent No. 11,142,549 Issues
2022-05-03	U.S. Patent No. 11,319,346 Issues
2022-07-18	Plaintiffs Receive Defendant's Notice Letter
2022-09-01	Complaint Filed

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

U.S. Patent No. 11,142,549 - "Ultra-pure agonists of guanylate cyclase C, method of making and using same," Issued October 12, 2021

The Invention Explained

• Problem Addressed: The patent specification notes that prior art methods for synthesizing and purifying peptides often result in products containing undesirable impurities, such as degradation products or process-related contaminants (e.g., trifluoroacetic acid, or TFA), which can compromise the final drug product's stability and manufacturability (’549 Patent, col. 3:28-36; col. 8:27-33).
• The Patented Solution: The invention describes a process for purifying the peptide plecanatide (identified as SEQ ID NO: 1) to achieve a high degree of purity and specific physical properties. The process involves steps such as using a polymeric adsorbent resin for desalination and employing specific solvent exchanges, which differ from conventional lyophilization (freeze-drying) and are intended to yield a final peptide product with very low levels of specific impurities and superior physical characteristics for tableting, such as improved bulk density and particle size distribution (’549 Patent, Abstract; col. 3:40-55; Fig. 5).
• Technical Importance: Achieving high purity and specific physical properties for a peptide active pharmaceutical ingredient is critical for ensuring lot-to-lot consistency, long-term stability, and efficient manufacturing of a uniform oral dosage form (’549 Patent, col. 101:63-col. 102:4).

Key Claims at a Glance

• The complaint asserts infringement of at least one claim without specification (Compl. ¶23). Independent claim 1 is representative:
• An oral formulation comprising:
  • (a) A purified peptide comprising the Guanylate Cyclase-C (GCC) agonist of amino acid sequence of SEQ ID NO: 1;
  • wherein the purified peptide comprises less than 0.05% trifluoroacetic acid (TFA) by weight of the purified peptide; and
  • (b) one or more pharmaceutically acceptable excipients, wherein the one or more pharmaceutically acceptable excipients comprise microcrystalline cellulose.
• The complaint reserves the right to assert other claims of the ’549 Patent (Compl. ¶24-25).

U.S. Patent No. 11,319,346 - "Ultra-pure agonists of guanylate cyclase C, method of making and using same," Issued May 3, 2022

The Invention Explained

• Problem Addressed: Similar to its parent patent, the ’346 Patent addresses the problem of impurities arising during peptide synthesis and purification, with a particular focus on "topoisomers"—molecules with the same chemical formula but different structural arrangements—which can be difficult to separate from the desired peptide and may have different biological properties (’346 Patent, col. 3:25-33; col. 6:21-29).
• The Patented Solution: The ’346 Patent claims oral formulations of plecanatide (SEQ ID NO: 1) characterized by a very low level of topoisomers. The specification describes purification processes, including specific chromatography and salt exchange steps, designed to remove these and other impurities, resulting in a highly pure and stable active ingredient for pharmaceutical use (’346 Patent, Abstract; col. 8:27-33; Fig. 6).
• Technical Importance: Controlling the level of isomers is a key challenge in peptide drug manufacturing, as the presence of even small amounts of unintended isomers can impact a drug's safety, efficacy, and stability profile (’346 Patent, col. 6:21-29).

Key Claims at a Glance

• The complaint asserts infringement of at least one claim without specification (Compl. ¶28). Independent claims 1 and 8 are representative of distinct compositions:
• Claim 1: An oral formulation comprising a purified peptide of SEQ ID NO: 1, wherein the formulation comprises less than 2% by weight of topoisomers.
• Claim 8: An oral formulation comprising (a) a purified peptide of SEQ ID NO: 1 with less than 300 ppm TFA and (b) microcrystalline cellulose as an excipient.
• The complaint reserves the right to assert other claims of the ’346 Patent (Compl. ¶29-30).

III. The Accused Instrumentality

Product Identification

• Defendant’s generic plecanatide oral tablets, 3 mg, which are the subject of ANDA No. 215686 filed with the U.S. FDA (Compl. ¶4, 14).

Functionality and Market Context

• The accused product is a proposed generic version of Plaintiffs’ branded drug, Trulance®, and is intended for the same therapeutic uses (Compl. ¶15). The complaint alleges that the ANDA submission contains data to establish that the generic product is the same as, or at least bioequivalent to, Trulance® (Compl. ¶19, 21). The act of infringement alleged is the filing of the ANDA itself, which seeks FDA approval for commercial manufacture and sale in the United States (Compl. ¶15).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint. The complaint does not contain detailed infringement contentions or claim charts, which is typical for an initial pleading in an ANDA case. The infringement theory is based on 35 U.S.C. § 271(e)(2), which defines the submission of an ANDA for a drug claimed in a patent as an act of infringement. The core allegation is that because Mylan seeks approval for a generic version of Trulance®, the product described in its ANDA will necessarily meet the limitations of the patents-in-suit, which are listed in the Orange Book for Trulance®.

• ’549 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
An oral formulation comprising: a) A purified peptide comprising the Guanylate Cyclase-C (GCC) agonist of amino acid sequence of SEQ ID NO: 1;	Defendant’s ANDA No. 215686 seeks approval to market "generic plecanatide oral tablets," which contains the peptide of SEQ ID NO: 1 (Compl. ¶4, 15).	¶4, 15, 21	col. 233:38-40
wherein the purified peptide comprises less than 0.05% trifluoroacetic acid (TFA) by weight of the purified peptide; and	As a generic version of Trulance®, the ANDA product is alleged to have the same characteristics as the branded product, which Plaintiffs assert meets this purity limitation (Compl. ¶21, 23).	¶21, 23	col. 233:41-43
b) one or more pharmaceutically acceptable excipients, wherein the one or more pharmaceutically acceptable excipients comprise microcrystalline cellulose.	Defendant’s product is an oral tablet formulation and, as a generic equivalent of Trulance®, is alleged to contain pharmaceutically acceptable excipients including microcrystalline cellulose (Compl. ¶15, 21).	¶15, 21	col. 233:44-47

• Identified Points of Contention: The primary dispute will be factual and evidentiary. A key question is whether Mylan’s proposed generic product, as detailed in its ANDA, actually meets the claimed purity limitation of less than 0.05% TFA. The litigation will likely focus on discovery related to Mylan's manufacturing process and the results of analytical testing on its finished drug product.

• ’346 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
An oral formulation comprising: a purified peptide comprising the Guanylate Cyclase-C (GCC) agonist of amino acid sequence of SEQ ID NO: 1;	Defendant’s ANDA No. 215686 seeks approval to market "generic plecanatide oral tablets," which contains the peptide of SEQ ID NO: 1 (Compl. ¶4, 15).	¶4, 15, 21	col. 236:53-56
wherein the formulation comprises less than 2% by weight of topoisomers relative to the weight of the purified peptide.	Because Defendant's product is intended to be a generic equivalent of Trulance®, Plaintiffs allege it will meet the same purity profile, including the claimed low level of topoisomers (Compl. ¶21, 28).	¶21, 28	col. 236:57-59

• Identified Points of Contention: The infringement analysis for the ’346 Patent will raise a significant technical question: what is the level of "topoisomers" in Mylan's proposed product? This will require detailed chemical analysis and may also trigger a legal dispute over the precise definition of the term "topoisomers" as used in the patent.

V. Key Claim Terms for Construction

• The Term: "purified peptide"

  • Context and Importance: This term appears in the preamble of the asserted claims of both patents. Its construction is critical because it may inform the scope of the claims. Practitioners may focus on this term to dispute whether it is merely descriptive or if it implies limitations based on the purification process detailed in the specification, rather than just the final product's characteristics.
  • Intrinsic Evidence for a Broader Interpretation: The body of the claims defines the peptide by its final purity characteristics (e.g., <0.05% TFA or <2% topoisomers), which may support an interpretation where any peptide meeting these objective purity criteria is a "purified peptide," regardless of the method used to produce it (’549 Patent, col. 233:41-43).
  • Intrinsic Evidence for a Narrower Interpretation: The specification extensively describes specific purification methods that are presented as inventive and essential to solving the problems of the prior art, such as using polymeric adsorbent resins and specific solvent precipitation steps instead of lyophilization (’549 Patent, Abstract; Fig. 5; col. 8:10-33). A party could argue that the term "purified peptide" should be limited to a peptide purified by these novel methods, not just any peptide that happens to meet the purity levels.

• The Term: "topoisomers"

  • Context and Importance: This term is the central limitation in claim 1 of the ’346 Patent. The infringement determination will depend entirely on measuring the quantity of these specific impurities. The case will likely require a precise, technical definition of which molecular variants of plecanatide qualify as "topoisomers."
  • Intrinsic Evidence for a Broader Interpretation: The specification discusses topoisomers in the context of general impurities to be removed, stating that "‘substantially’ free of topoisomers means that the topoisomer content... is preferably less than 2%," suggesting it is a known class of impurities (’346 Patent, col. 6:21-25). This could support a reading that includes any structurally isomeric forms.
  • Intrinsic Evidence for a Narrower Interpretation: The patent identifies a specific degradation product, "iso-Asp2-plecanatide," as an example of an impurity that is measured (’346 Patent, col. 6:13-16). A defendant may argue that "topoisomers" should be construed narrowly to include only this specific, identified variant or other isomers that are explicitly described or identifiable using the analytical methods disclosed in the patent.

VI. Other Allegations

• Indirect Infringement: The complaint alleges that Mylan will induce and contribute to the infringement of the patents-in-suit (Compl. ¶25, 30). In the context of an ANDA case, this allegation is typically based on the argument that the defendant’s proposed product label will instruct physicians and patients to administer the drug, which itself constitutes direct infringement of the formulation claims.
• Willful Infringement: The complaint does not use the term "willful infringement." However, it requests that the court declare the case "exceptional" under 35 U.S.C. § 285, which allows for the award of attorney's fees (Compl. Prayer ¶6). The factual basis for this appears to be Mylan's knowledge of the patents via their Orange Book listing and its alleged failure to provide a "full and detailed explanation regarding any non-infringement defense" in its Paragraph IV notice letter (Compl. ¶12, 20).

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

This ANDA litigation appears poised to center on the technical details of the accused generic product and the proper scope of the patent claims. The key questions for the court will likely be:

1. A central evidentiary question will be one of analytical proof: can Plaintiffs demonstrate, through chemical analysis of Mylan’s proposed generic product, that it in fact contains the claimed low levels of specific impurities (e.g., less than 0.05% TFA or less than 2% topoisomers) required by the asserted claims?
2. A core issue of claim construction will be one of process vs. product: must the term "purified peptide" be limited to a peptide made by the novel purification processes described in the specification, or does it simply define a final product with certain measurable characteristics, regardless of how it was made?
3. A further question of claim construction will involve definitional precision: what is the exact scope of the term "topoisomers"? The outcome of the infringement analysis for the ’346 patent may turn on whether this term is interpreted broadly to cover a class of related isomers or narrowly to cover only specific variants identified in the patent.