Bausch Health Ireland Ltd v. Aurobindo Pharma Ltd

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Bausch Health Ireland Limited (Ireland) and Salix Pharmaceuticals, Inc. (California/New Jersey)
  • Defendant: Aurobindo Pharma Limited (India); Aurobindo Pharma USA Inc. (Delaware/New Jersey); and Auro Peptides Ltd. (India)
  • Plaintiff’s Counsel: Gibbons P.C.; Finnegan, Henderson, Farabow, Garrett & Dunner, LLP
• Case Identification: 2:23-cv-00170, D.N.J., 01/12/2023
• Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Aurobindo Pharma USA Inc. maintains its principal place of business in the district, and because the district is a likely destination for the accused generic drug products.
• Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) to the U.S. Food and Drug Administration (FDA) for generic plecanatide oral tablets constitutes an act of infringement of eight U.S. patents.
• Technical Context: The technology concerns plecanatide, a synthetic peptide analog of human uroguanylin, used for treating gastrointestinal disorders such as chronic idiopathic constipation and irritable bowel syndrome with constipation.
• Key Procedural History: This Hatch-Waxman litigation was triggered by Plaintiffs’ receipt on November 28, 2022, of a Notice Letter regarding Defendants' ANDA submission, which included Paragraph IV certifications against the patents-in-suit. The patents are listed in the FDA's "Orange Book" as covering Plaintiffs' plecanatide product, Trulance®.

Case Timeline

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

U.S. Patent No. 7,041,786 - Guanylate Cyclase Receptor Agonists for the Treatment of Tissue Inflammation and Carcinogenesis

The Invention Explained

• Problem Addressed: The patent describes an imbalance between cell proliferation and apoptosis (programmed cell death) in the gastrointestinal (GI) tract as a promoter of inflammation and carcinogenesis (e.g., colon cancer). It notes that the production of uroguanylin and guanylin, peptides that help regulate this balance, is often decreased in pre-cancerous polyps and tumor tissues. (’786 Patent, col. 3:25-30, 3:63-67).
• The Patented Solution: The invention provides peptide agonists of the guanylate cyclase receptor, which are designed to stimulate the intracellular production of cyclic guanosine monophosphate (cGMP). This stimulation is intended to restore the homeostatic balance between cell proliferation and apoptosis, thereby providing a therapeutic approach to treating GI inflammation and cancer. (’786 Patent, Abstract; col. 4:1-14).
• Technical Importance: This technology provided a therapeutic strategy for treating GI disorders by targeting the cGMP signaling pathway to control cellular growth and death, rather than using traditional cytotoxic chemotherapy. (Compl. ¶17; ’786 Patent, col. 3:63-67).

Key Claims at a Glance

• The complaint asserts infringement of at least one claim (Compl. ¶38). The patent's first independent claim is representative:
• Claim 1:
  • A peptide
  • consisting of the amino acid sequence of SEQ ID NO:20.

---

U.S. Patent No. 9,610,321 - Formulations of Guanylate Cyclase C Agonists and Methods of Use

The Invention Explained

• Problem Addressed: The patent identifies a need for effective low-dose oral formulations of Guanylate Cyclase-C (GCC) agonist peptides. It notes that such peptides can be subject to chemical and physical instability, which presents challenges for creating a viable and stable oral drug product. (’321 Patent, col. 3:19-27).
• The Patented Solution: The invention provides specific low-dose oral dosage formulations of GCC agonist peptides, including plecanatide, that are stabilized against degradation. The solution involves combining the peptide with specific excipients, such as an "inert low moisture carrier" and a lubricant, to maintain the peptide's purity and stability over time. (’321 Patent, Abstract; Summary of the Invention, col. 3:28-44).
• Technical Importance: This invention enabled the development of a stable, oral, low-dose tablet for administering plecanatide, which is critical for the long-term treatment of chronic conditions like chronic idiopathic constipation (CIC). (Compl. ¶18; ’321 Patent, col. 3:28-35).

Key Claims at a Glance

• The complaint asserts infringement of at least one claim (Compl. ¶49). The patent's first independent claim is representative:
• Claim 1:
  • A method for treating chronic constipation in a human subject
  • comprising orally administering to said human subject a composition consisting of:
  • a unit dose of 3.0 mg or 6.0 mg of a peptide consisting of SEQ ID NO:1 wherein said peptide is a [4,12; 7,15] bicycle,
  • an inert low moisture carrier,
  • and a lubricant,
  • wherein the peptide has a chromatographic purity of no less than 91% after storage for at least three months.

U.S. Patent No. 9,616,097 - Formulations of Guanylate Cyclase C Agonists and Methods of Use

• Technology Synopsis: The patent claims specific oral dosage formulations of a GCC agonist peptide. The invention is directed to the composition itself, focusing on creating a stable, low-dose oral formulation by combining the peptide with particular types of carriers and lubricants to ensure long-term purity. (’097 Patent, Abstract).
• Asserted Claims: At least one claim is asserted. Claim 1 is an independent claim. (Compl. ¶60).
• Accused Features: The accused features are Defendants' generic plecanatide oral tablets, which are alleged to be formulations that infringe the patent claims. (Compl. ¶61).

U.S. Patent No. 9,919,024 - Formulations of Guanylate Cyclase C Agonists and Methods of Use

• Technology Synopsis: The patent claims methods of treating chronic constipation or alleviating its symptoms by orally administering a specific low-dose formulation of a GCC agonist peptide. The invention is directed to the therapeutic use of the stable formulation. (’024 Patent, Abstract).
• Asserted Claims: At least one claim is asserted. Claim 1 is an independent claim. (Compl. ¶71).
• Accused Features: The accused instrumentality is the act of seeking FDA approval to market a generic plecanatide tablet for the treatment of chronic constipation, which would induce infringement of the claimed methods. (Compl. ¶¶ 71, 73).

U.S. Patent No. 9,925,231 - Formulations of Guanylate Cyclase C Agonists and Methods of Use

• Technology Synopsis: The patent claims specific oral dosage formulations containing a GCC agonist peptide. The claims focus on the composition, requiring specific characteristics such as the peptide structure, a low moisture carrier, a lubricant, and a defined level of chromatographic purity after storage, to ensure the stability of the final drug product. (’231 Patent, Abstract).
• Asserted Claims: At least one claim is asserted. Claim 1 is an independent claim. (Compl. ¶82).
• Accused Features: The accused features are Defendants' generic plecanatide oral tablets, alleged to be infringing formulations. (Compl. ¶83).

U.S. Patent No. 10,011,637 - Ultra-Pure Agonists of Guanylate Cyclase C, Method of Making and Using Same

• Technology Synopsis: The patent is directed to a purified peptide, plecanatide, having specific characteristics relating to purity and physical properties, such as bulk density, particle size, and low levels of specific impurities like acetamide. It also covers processes for purifying the peptide to achieve these characteristics. (’637 Patent, Abstract).
• Asserted Claims: At least one claim is asserted. Claims 1 and 14 are independent claims. (Compl. ¶93).
• Accused Features: The accused feature is the purified plecanatide peptide used as the active pharmaceutical ingredient in Defendants' generic tablets. (Compl. ¶94).

U.S. Patent No. 11,142,549 - Ultra-Pure Agonists of Guanylate Cyclase C, Method of Making and Using Same

• Technology Synopsis: The patent claims oral formulations comprising a purified GCC agonist peptide (plecanatide) with a very low level of trifluoroacetic acid (TFA), combined with one or more excipients. This invention addresses the problem of residual impurities from the synthesis and purification process. (’549 Patent, Abstract).
• Asserted Claims: At least one claim is asserted. Claim 1 is an independent claim. (Compl. ¶105).
• Accused Features: The accused feature is the formulation of Defendants' generic plecanatide tablets, which is alleged to comprise the claimed purified peptide with low TFA levels. (Compl. ¶105).

U.S. Patent No. 11,319,346 - Ultra-Pure Agonists of Guanylate Cyclase C, Method of Making and Using Same

• Technology Synopsis: The patent claims oral formulations comprising a purified GCC agonist peptide (plecanatide) characterized by having a low level of topoisomers, which are isomeric impurities. The invention provides a formulation with high purity to ensure safety and efficacy. (’346 Patent, Abstract).
• Asserted Claims: At least one claim is asserted. Claims 1 and 8 are independent claims. (Compl. ¶116).
• Accused Features: The accused feature is the formulation of Defendants' generic plecanatide tablets, alleged to contain plecanatide with the claimed low level of topoisomers. (Compl. ¶116).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Defendants' generic plecanatide oral tablets, 3 mg, for which Aurobindo Pharma Limited submitted ANDA No. 217007 to the FDA for approval (Compl. ¶¶ 6, 27, 31).

Functionality and Market Context

The complaint alleges that the accused product is a generic version of Plaintiffs' Trulance® brand plecanatide tablets (Compl. ¶28). The product is an oral tablet intended for the same therapeutic uses as Trulance®, such as treating chronic constipation (Compl. ¶18). The ANDA submission necessarily contains data intended to demonstrate that the generic product is bioequivalent to Trulance® (Compl. ¶32). The complaint alleges that Defendants intend to commercially manufacture, use, and sell the product in the United States upon receiving FDA approval (Compl. ¶28). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not contain a claim chart or detailed infringement allegations. The infringement theory is based on 35 U.S.C. § 271(e)(2), where the submission of an ANDA for a drug claimed in a patent is a statutory act of infringement. The complaint alleges the accused generic product is "the same, or substantially the same, as Trulance®," which embodies the patented inventions (Compl. ¶35).

• '786 Patent Infringement Allegations

• '321 Patent Infringement Allegations

• Identified Points of Contention:
  • Factual & Analytical Questions: A primary factual question will be whether the active pharmaceutical ingredient in Defendants' product is identical to the peptide claimed in the ’786 Patent and whether its formulation and stability characteristics meet the specific quantitative limitations of claims in the other patents (e.g., the '321 Patent's purity-after-storage limitation).
  • Scope Questions: For the formulation patents, including the '321 Patent, a key legal question may concern the proper construction of terms like "inert low moisture carrier." The dispute may center on whether the specific excipients used in Defendants' formulation fall within the scope of these terms as they are defined in the patents and understood by a person of ordinary skill in the art.

V. Key Claim Terms for Construction

• The Term: "consisting of" (’786 Patent, Claim 1)

• Context and Importance: This term is a closed transitional phrase in claim drafting. Its construction is critical because it dictates that the claimed peptide must contain only the amino acids of SEQ ID NO:20 and nothing more. If Defendants' plecanatide contains any additional moieties or amino acid substitutions, it might not infringe this claim, making the definition of this term central to the dispute over the ’786 Patent.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Narrower Interpretation: The use of "consisting of" is strong intrinsic evidence for a narrow, closed-ended scope, excluding any unlisted elements. This interpretation is the standard default in patent law. The patent does not appear to provide any special definitions that would broaden the term.

• The Term: "inert low moisture carrier" (’321 Patent, Claim 1)

• Context and Importance: This term is a key component of the claimed formulation. The infringement analysis for the '321 Patent and related formulation patents will depend heavily on whether the carrier(s) used in Defendants' generic product meet this definition. Practitioners may focus on this term because designing a formulation with a different type of carrier could be a non-infringement strategy.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The specification provides a list of potential carriers, including "mannitol, lactose, microcrystalline cellulose, or starch," which could be argued to be an exemplary, non-limiting list of substances that qualify as "inert low moisture carriers." (’321 Patent, col. 5:2-4).
  • Evidence for a Narrower Interpretation: The patent provides a specific definition for "low moisture," stating the carrier has "a water content of less than 1% w/w." (’321 Patent, col. 16:1-3). A defendant could argue that its carrier does not meet this quantitative limit or that the term "inert" has a specific technical meaning that excludes the excipients used in their formulation.

VI. Other Allegations

• Indirect Infringement: The complaint alleges Defendants will contributorily infringe and induce infringement of the asserted patents (Compl. ¶¶ 40, 51, 62, etc.). For method patents such as the ’321 Patent and ’024 Patent, the allegation is based on the premise that Defendants' product label and marketing materials will instruct physicians and patients to administer the generic drug for the claimed therapeutic purposes, thereby encouraging direct infringement by end-users.
• Willful Infringement: The complaint does not explicitly allege "willful" infringement. However, it requests a declaration that the case is "exceptional" under 35 U.S.C. § 285, which allows for the award of attorney's fees (Compl., Prayer for Relief ¶12). The basis for this appears to be Defendants' knowledge of the patents, evidenced by their filing of a Paragraph IV certification, a formal statement that the patents are invalid or not infringed (Compl. ¶29).

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

The resolution of this case will likely depend on the court's findings on several core issues. The central questions presented by the complaint are:

• Claim Construction and Formulation Scope: A primary issue will be one of definitional scope for the formulation patents. Can claim terms such as "inert low moisture carrier" and specific purity limitations (e.g., "less than 2% by weight of topoisomers" in the '346 patent) be construed to read on the specific excipients and impurity profiles of Defendants' proposed generic product?
• Doctrine of Equivalents: Given the potential for non-literal infringement arguments in pharmaceutical cases, a key question will be one of technical equivalence. If Defendants' formulation does not literally meet the claim limitations, does it contain components that perform substantially the same function in substantially the same way to achieve the same result as the claimed invention?
• Infringement by ANDA Submission: The fundamental question under the Hatch-Waxman Act is whether the product that will be sold under the ANDA, if approved, would infringe the asserted patents. This will involve a detailed comparison of the proposed generic product's composition, formulation, and labeled use against the construed claims of the eight patents-in-suit.