DCT

2:23-cv-03333

Bausch Health Ireland Ltd v. MSN Laboratories Private LTD.

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:23-cv-03333, D.N.J., 06/16/2023
  • Venue Allegations: Venue is alleged to be proper as to MSN Pharmaceuticals Inc. because its principal place of business is in the District of New Jersey. Venue is alleged against MSN Laboratories Private Ltd., a foreign corporation, on the basis that it has purposefully conducted business in the district and the district is a likely destination for its generic products.
  • Core Dispute: Plaintiffs allege that Defendants' Abbreviated New Drug Application (ANDA) to market a generic version of the gastrointestinal drug Trulance® constitutes an act of infringement of two patents covering highly purified formulations of the active ingredient, plecanatide.
  • Technical Context: The technology concerns methods for purifying peptide-based drug substances to achieve specific, low levels of process-related impurities, which is critical for ensuring the safety, stability, and efficacy of the final oral dosage form.
  • Key Procedural History: This is a Hatch-Waxman action triggered by Defendants' filing of ANDA No. 215780, seeking FDA approval for generic plecanatide tablets. The patents-in-suit are listed in the FDA's "Orange Book" for Trulance®. Plaintiffs state they received a Paragraph IV Notice Letter from Defendants on May 2, 2023, asserting non-infringement of certain claims based on the level of trifluoroacetic acid (TFA) in the proposed generic product.

Case Timeline

Date Event
2013-06-05 Earliest Priority Date for ’549 and ’346 Patents
2017-01-19 FDA Approval of Trulance® (NDA No. 208745)
2021-10-12 U.S. Patent No. 11,142,549 Issued
2022-05-03 U.S. Patent No. 11,319,346 Issued
2023-05-02 Plaintiffs Receive Defendants’ Paragraph IV Notice Letter
2023-06-16 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 describes challenges in the synthesis of peptide-based pharmaceuticals, which can result in low yields and undesirable levels of impurities, such as process-related contaminants or structurally similar but inactive "topoisomers" ('549 Patent, col. 3:28-36).
  • The Patented Solution: The invention provides processes for purifying a guanylate cyclase-C (GCC) agonist peptide (plecanatide) to achieve a high degree of purity and specific physical characteristics. The process involves steps like solvent exchange and lyophilization to reduce impurities and create a product suitable for pharmaceutical formulation ('549 Patent, Abstract; col. 3:40-53). The resulting purified peptide is then claimed in an oral formulation with specific, very low limits on certain impurities.
  • Technical Importance: Achieving high purity and controlling the physical form of a peptide active pharmaceutical ingredient (API) is critical for creating a stable, safe, and effective oral drug product with consistent dosing and bioavailability ('549 Patent, col. 101:59-67).

Key Claims at a Glance

  • The complaint asserts infringement of claims 1-6 ('Compl. ¶25). Independent claim 1 is representative:
  • Claim 1 Elements:
    • 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.

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 the ’549 patent, this patent addresses the need to control impurities generated during the synthesis and purification of peptide drugs ('346 Patent, col. 3:20-27).
  • The Patented Solution: The invention claims oral formulations of purified plecanatide (SEQ ID NO: 1) defined by different purity characteristics. The claims focus on limiting the amount of "topoisomers" (structurally related impurities) in the formulation (Claim 1) or setting a different quantitative limit for TFA impurity than the ’549 patent (Claim 8) ('346 Patent, Abstract; col. 4:16-20).
  • Technical Importance: Limiting specific impurities like topoisomers and TFA is essential for regulatory approval and ensuring that the therapeutic effect of the drug is consistent and its safety profile is well-defined.

Key Claims at a Glance

  • The complaint asserts infringement of claims 8-12 ('Compl. ¶25). Independent claim 8 is representative of this group:
  • Claim 8 Elements:
    • 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 0.5% trifluoroacetic acid (TFA) by weight of the purified peptide; and
    • (b) one or more pharmaceutically acceptable excipients.
  • The complaint also notes that Defendants' notice letter failed to provide a non-infringement explanation for claims 1-7 of the ’346 patent ('Compl. ¶25).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is "MSN's generic plecanatide oral tablets, 3 mg," which is the subject of Abbreviated New Drug Application (ANDA) No. 215780 filed with the FDA ('Compl. ¶¶6, 21).

Functionality and Market Context

The product is a proposed generic version of Plaintiffs' branded drug, Trulance®, and is intended to be therapeutically equivalent. The complaint alleges MSN's ANDA 'contains the required bioavailability and/or bioequivalence data' and that the proposed generic tablets 'are the same, or substantially the same, as Trulance®' ('Compl. ¶¶24, 26). The product is intended for commercial manufacture, use, and sale in the United States upon receiving FDA approval ('Compl. ¶21).

IV. Analysis of Infringement Allegations

The complaint's infringement allegations are based on the act of filing the ANDA under 35 U.S.C. § 271(e)(2). The core theory is that the product described in the ANDA, if approved and marketed, would meet all the limitations of the asserted patent claims. No probative visual evidence provided in complaint.

U.S. Patent No. 11,142,549 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
An oral formulation MSN's ANDA No. 215780 describes an oral tablet formulation. ¶21, ¶23 col. 233:41-42
comprising: (a) a purified peptide comprising the Guanylate Cyclase-C (GCC) agonist of amino acid sequence of SEQ ID NO: 1 The ANDA product is a generic version of Trulance® and necessarily contains the plecanatide peptide of SEQ ID NO: 1. ¶21, ¶26 col. 233:42-43
wherein the purified peptide comprises less than 0.05% trifluoroacetic acid (TFA) by weight of the purified peptide The complaint alleges that upon information and belief, MSN's purified peptide would infringe, disputing the non-infringement position taken in MSN's notice letter. ¶25 col. 233:43-45
and (b) one or more pharmaceutically acceptable excipients, wherein the one or more pharmaceutically acceptable excipients comprise microcrystalline cellulose. The complaint does not provide specific details on the excipients in MSN's ANDA product, but this is a common excipient for oral tablets. ¶26 col. 233:45-48

U.S. Patent No. 11,319,346 Infringement Allegations

Claim Element (from Independent Claim 8) Alleged Infringing Functionality Complaint Citation Patent Citation
An oral formulation comprising: MSN's ANDA No. 215780 describes an oral tablet formulation. ¶21, ¶23 col. 236:53
(a) a purified peptide comprising the Guanylate Cyclase-C (GCC) agonist of amino acid sequence of SEQ ID NO: 1 The ANDA product is a generic version of Trulance® and necessarily contains the plecanatide peptide of SEQ ID NO: 1. ¶21, ¶26 col. 236:54-56
wherein the purified peptide comprises less than 0.5% trifluoroacetic acid (TFA) by weight of the purified peptide The complaint alleges that upon information and belief, MSN's purified peptide would infringe, despite MSN's assertion of non-infringement based on TFA levels. ¶25 col. 236:56-59
and (b) one or more pharmaceutically acceptable excipients. The ANDA product necessarily contains excipients to form an oral tablet. ¶26 col. 236:59-60
  • Identified Points of Contention:
    • Quantitative Factual Dispute: The central dispute identified in the complaint revolves around a specific, measurable quantity: the weight percentage of trifluoroacetic acid (TFA) in the purified peptide. The complaint explicitly states that MSN's non-infringement defense for claims in both patents is based on "recited levels of trifluoroacetic acid (TFA)" (Compl. ¶25). The case will likely depend on factual evidence from MSN's ANDA submission detailing the precise specification of its drug product.
    • Methodological Questions: A potential underlying dispute may concern the analytical methods used to quantify trace impurities like TFA. The validity and precision of the testing methodology (e.g., high-performance liquid chromatography) used to certify the purity of the ANDA product could become a key technical question if the parties' measurements yield different results.

V. Key Claim Terms for Construction

The dispute appears to be more factual than linguistic, centering on whether the accused product meets specific quantitative thresholds. However, the construction of these quantitative terms, particularly how they are to be measured, will be critical.

  • The Term: "less than 0.05% trifluoroacetic acid (TFA) by weight of the purified peptide" ('549 Patent, Claim 1)
  • Context and Importance: This term sets a precise, stringent upper limit for a specific process-related impurity. Infringement of the ’549 patent hinges entirely on whether MSN's product meets this negative limitation. Practitioners may focus on this term because the complaint identifies it as the basis for MSN's non-infringement argument ('Compl. ¶25), making it the central battleground.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The term itself is quantitative and appears unambiguous. A party arguing for a straightforward application might point out that the patent does not specify a particular or unconventional method of measurement, suggesting any standard, scientifically accepted method for quantifying TFA should apply.
    • Evidence for a Narrower Interpretation: A party might argue the term must be interpreted in the context of the patent's examples and described analytical methods, such as the UPLC analysis mentioned ('549 Patent, col. 4:1-3). Example 6 ('549 Patent, Table XX, col. 105-106) provides measured TFA levels in precipitated (<28 ppm, or <0.0028%) and lyophilized (356 ppm, or 0.0356%) batches, both of which are well below the 0.05% (500 ppm) claim limit, demonstrating the feasibility and context of the claimed purity level.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Defendants will contributorily infringe and/or induce infringement through the future marketing and sale of the generic product ('Compl. ¶¶31, 42). In the ANDA context, an allegation of induced infringement is typically supported by the proposed drug label, which would instruct physicians and patients to use the drug in a manner that directly infringes.
  • Willful Infringement: The complaint does not use the term "willful infringement." However, it requests that the court 'Declare this to be an exceptional case under 35 U.S.C. §§ 285 and 271(e)(4)' and award attorneys' fees ('Compl., Prayer for Relief ¶6). An exceptional case finding can be based on litigation misconduct or the weakness of the losing party's case. The knowledge element is established by the filing of a Paragraph IV certification, which constitutes an admission of knowledge of the asserted patents.

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

  • A core issue will be one of quantitative fact: Does the plecanatide drug product, as specified in Defendants' confidential ANDA submission, contain an amount of trifluoroacetic acid (TFA) that is definitively above or below the precise numerical thresholds of "less than 0.05%" ('549 Patent) and "less than 0.5%" ('346 Patent)? The outcome of the infringement analysis for the most heavily contested claims depends entirely on this factual determination.
  • A related evidentiary question will be one of analytical methodology: If the parties' measurements of impurity levels conflict, the case may turn on which analytical testing method is deemed most appropriate and reliable for measuring trace contaminants in the accused formulation. The court may need to resolve whether the methodology used by the defendant, as described in its ANDA, is consistent with the methods contemplated by the patents.
  • A third question concerns claim scope and prosecution history: While not detailed in the complaint, the prosecution histories of the patents will be examined for any disclaimers or definitions made by the patentee to secure the claims. Arguments may arise regarding whether the patentee narrowed the scope of how these quantitative limits should be interpreted or measured, potentially creating a path for non-infringement.