DCT

1:24-cv-09512

Salix Pharma Inc v. Zydus Pharma USA Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-09512, D.N.J., 09/27/2024
  • Venue Allegations: Venue is alleged as proper because Defendant Zydus Pharmaceuticals (USA) Inc. is a corporation organized and existing under the laws of New Jersey and is subject to personal jurisdiction in the district.
  • Core Dispute: Plaintiff alleges that Defendant's filing of an Abbreviated New Drug Application for a generic version of the drug Xifaxan® (rifaximin) infringes seven patents related to methods of treating Irritable Bowel Syndrome and specific polymorphic forms of the active ingredient rifaximin.
  • Technical Context: The dispute centers on rifaximin, a minimally-absorbed oral antibiotic used to treat various gastrointestinal conditions, which represents a significant pharmaceutical market.
  • Key Procedural History: The action was initiated under the Hatch-Waxman Act following Defendant's August 15, 2024, notification letter, which included a Paragraph IV certification asserting non-infringement, unenforceability, or invalidity of the patents-in-suit, all of which are listed in the U.S. Food and Drug Administration's "Orange Book" for the brand-name drug Xifaxan®.

Case Timeline

Date Event
2004-05-25 FDA approval of Xifaxan® 200 mg tablets
2005-03-03 Earliest Priority Date for ’196, ’949, ’904, ’968, and ’763 Patents
2008-02-26 Earliest Priority Date for ’571 and ’912 Patents
2010-03-24 FDA approval of Xifaxan® 550 mg tablets
2012-06-05 U.S. Patent No. 8,193,196 Issued
2013-08-27 U.S. Patent No. 8,518,949 Issued
2014-06-03 U.S. Patent No. 8,741,904 Issued
2016-03-01 U.S. Patent No. 9,271,968 Issued
2020-07-07 U.S. Patent No. 10,703,763 Issued
2023-01-31 U.S. Patent No. 11,564,912 Issued
2023-10-10 U.S. Patent No. 11,779,571 Issued
2024-08-15 Date of Defendant's Paragraph IV Notice Letter
2024-09-27 Complaint Filing Date

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

U.S. Patent No. 11,779,571 - "Methods for Treating Irritable Bowel Syndrome (IBS)"

Issued October 10, 2023

The Invention Explained

  • Problem Addressed: The patent addresses the need for effective methods of treating bowel diseases such as Irritable Bowel Syndrome (IBS) and diarrhea-predominant IBS (dIBS) ('571 Patent, col. 1:41-55).
  • The Patented Solution: The invention provides methods for treating symptoms of IBS by administering a specific dosage regimen of rifaximin, a rifamycin class antibiotic. The specification highlights the concept of achieving a "durability of response," where a patient who responds to treatment continues to experience relief from symptoms even after the treatment course has ended ('571 Patent, col. 2:41-48). The patent describes clinical study designs and outcomes related to this durable effect (e.g., '571 Patent, FIG. 3; col. 23:9-31).
  • Technical Importance: The approach is presented as significant for providing long-term symptom relief from a chronic condition with a short, acute course of antibiotic treatment, potentially reducing the need for continuous medication.

Key Claims at a Glance

  • The complaint does not identify specific claims asserted against the '571 Patent, alleging infringement of "one or more claims" (Compl. ¶48). Claim 1 is the first independent claim.
  • Essential elements of Independent Claim 1 include:
    • A method of treating bloating associated with diarrhea-predominant irritable bowel syndrome (dIBS) in a female subject
    • comprising administering, 550 mg of rifaximin TID [three times a day] for 14 days to the female subject
    • thereby treating bloating associated with dIBS in the female subject
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 11,564,912 - "Methods for Treating Irritable Bowel Syndrome (IBS)"

Issued January 31, 2023

The Invention Explained

  • Problem Addressed: Similar to the '571 Patent, this patent addresses the treatment of bowel diseases, including IBS and its associated symptoms like pain, diarrhea, and bloating ('912 Patent, col. 1:41-55).
  • The Patented Solution: The invention is a method of treating IBS symptoms through the administration of rifaximin. The specification discusses clinical data suggesting that specific patient populations, including females, may experience a differential response to the treatment ('912 Patent, Table 1; col. 13:58-14:15).
  • Technical Importance: This patent focuses on providing targeted treatment methods for specific subpopulations of IBS patients, potentially allowing for more tailored therapeutic strategies.

Key Claims at a Glance

  • The complaint does not identify specific claims asserted against the '912 Patent, alleging infringement of "one or more claims" (Compl. ¶60). Claim 1 is the first independent claim.
  • Essential elements of Independent Claim 1 include:
    • A method of treating one or more symptoms of irritable bowel syndrome (IBS) in a female subject
    • said method comprising administering, 550 mg of rifaximin TID for 14 days to the female subject
    • thereby treating one or more symptoms of IBS in the female subject
  • The complaint does not explicitly reserve the right to assert dependent claims.

Multi-Patent Capsule: Polymorph Patents

  • U.S. Patent No. 8,193,196 ("Polymorphous Forms of Rifaximin..."), issued June 5, 2012

    • Technology Synopsis: The patent describes specific crystalline polymorphous forms of rifaximin, identified as forms δ (delta) and ε (epsilon), and processes for their production ('196 Patent, Abstract). The existence of distinct polymorphs can affect a drug's properties, such as bioavailability and stability ('196 Patent, col. 2:10-24).
    • Asserted Claims: The complaint alleges infringement of "one or more claims" (Compl. ¶72).
    • Accused Features: The Zydus ANDA product is accused of being or containing a polymorphic form of rifaximin that infringes the patent (Compl. ¶¶ 71-72).

  • U.S. Patent No. 8,518,949 ("Polymorphous Forms of Rifaximin..."), issued August 27, 2013

    • Technology Synopsis: This patent is related to the ’196 Patent and also claims specific polymorphous forms of rifaximin ('949 Patent, Abstract). It further details processes for producing these forms and their use in medicinal preparations.
    • Asserted Claims: The complaint alleges infringement of "one or more claims" (Compl. ¶84).
    • Accused Features: The Zydus ANDA product is accused of infringing by comprising a claimed polymorphic form of rifaximin (Compl. ¶¶ 83-84).

  • U.S. Patent No. 8,741,904 ("Polymorphous Forms of Rifaximin..."), issued June 3, 2014

    • Technology Synopsis: Also related to the family of polymorph patents, this patent discloses specific crystalline forms of rifaximin and methods of using them to treat bacterial activity in the gastrointestinal tract ('904 Patent, col. 10:1-26).
    • Asserted Claims: The complaint alleges infringement of "one or more claims" (Compl. ¶96).
    • Accused Features: The Zydus ANDA Product is alleged to be a composition containing a claimed polymorphic form of rifaximin (Compl. ¶¶ 95-96).

  • U.S. Patent No. 9,271,968 ("Polymorphous Forms of Rifaximin..."), issued March 1, 2016

    • Technology Synopsis: This patent claims compositions comprising rifaximin polymorphic forms. It continues the focus on specific crystalline structures of the rifaximin active pharmaceutical ingredient ('968 Patent, Abstract).
    • Asserted Claims: The complaint alleges infringement of "one or more claims" (Compl. ¶108).
    • Accused Features: The Zydus ANDA Product is accused of being a composition comprising rifaximin that infringes the patent's claims (Compl. ¶¶ 107-108).

  • U.S. Patent No. 10,703,763 ("Polymorphous Forms of Rifaximin..."), issued July 7, 2020

    • Technology Synopsis: This patent describes and claims methods of treating bacterial activity in the gastrointestinal tract using pharmaceutical compositions that comprise specific rifaximin polymorphs, such as form δ ('763 Patent, col. 9:1-12).
    • Asserted Claims: The complaint alleges infringement of "one or more claims" (Compl. ¶120).
    • Accused Features: Zydus's manufacture and the intended use of its ANDA Product are alleged to infringe the claimed methods (Compl. ¶¶ 119-121).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Defendant's generic rifaximin 550 mg tablets, for which it seeks FDA approval via Abbreviated New Drug Application (ANDA) No. 218650 (the "ANDA Product") (Compl. ¶2).

Functionality and Market Context

  • The ANDA Product is a generic version of Plaintiff's Xifaxan® 550 mg tablets (Compl. ¶1). The complaint alleges that Zydus seeks FDA approval for the ANDA Product for the indication of treating irritable bowel syndrome with diarrhea (IBS-D) in adults (Compl. ¶32). As a generic drug, the ANDA Product is intended to be therapeutically equivalent to the brand-name product and will compete directly with it upon market entry (Compl. ¶1).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

The complaint does not contain a claim chart or specify which claims of the asserted patents are infringed. The analysis below is based on representative independent Claim 1 of the '571 and '912 Patents and the general allegations in the complaint.

'571 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating bloating associated with diarrhea-predominant irritable bowel syndrome (dIBS)... Defendant is alleged to seek FDA approval for its ANDA Product for the indication of treating irritable bowel syndrome with diarrhea in adults. ¶32 col. 7:1-8
...in a female subject... The complaint alleges on information and belief that the ANDA Product will be prescribed to human patients, which would include female subjects, for its approved indication. ¶49 col. 7:1-8
...comprising administering, 550 mg of rifaximin TID for 14 days to the female subject... Defendant's ANDA is for a 550 mg rifaximin tablet. The complaint alleges that upon approval, the product will be prescribed and administered to patients, which would induce infringement of the claimed method. ¶¶31, 49 col. 7:1-8

'912 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating one or more symptoms of irritable bowel syndrome (IBS)... Defendant is alleged to seek FDA approval for its ANDA Product for the indication of treating irritable bowel syndrome with diarrhea in adults. ¶32 col. 45:5-11
...in a female subject... The complaint alleges that the ANDA Product will be prescribed to human patients, including females, to relieve IBS symptoms. ¶61 col. 45:5-11
...said method comprising administering, 550 mg of rifaximin TID for 14 days to the female subject... The ANDA is for a 550 mg tablet. The complaint alleges that the intended use, guided by the product label, will result in administration to patients that constitutes infringement. ¶¶58, 61 col. 45:5-11
  • Identified Points of Contention:
    • Scope Questions (Method Patents): The asserted independent claims of the '571 and '912 patents are directed specifically to treating "a female subject." A central issue may be whether Defendant's proposed product label, by seeking a general indication for "adults" with IBS-D (Compl. ¶32), actively encourages or instructs physicians to use the drug in the specific manner required by the claims, or whether such use is merely a foreseeable but not induced outcome. This raises the question of whether Defendant can "carve out" the patented method from its label to avoid inducement.
    • Technical Questions (Polymorph Patents): A primary factual dispute for the '196, '949, '904, '968, and '763 patents will concern the physical characteristics of the ANDA Product's active ingredient. The complaint does not and cannot, at the pleading stage, provide evidence of the actual crystalline structure of Defendant's rifaximin. The core question for the court will be whether the specific polymorph(s) present in the ANDA Product fall within the scope of the asserted claims, which will depend on analytical evidence (e.g., X-ray powder diffraction data) exchanged during discovery.

V. Key Claim Terms for Construction

  • The Term: "treating"

    • Context and Importance: This term appears in the preambles of the independent claims of the method-of-use patents ('571 Patent, Claim 1; '912 Patent, Claim 1). Its construction is critical because infringement of a method claim requires that all steps of the method are performed. The definition of "treating" will determine what patient outcomes must be achieved or intended for infringement to occur.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification of the '912 patent states that the disclosed methods are for "preventing, ameliorating and/or treating bowel diseases" and that symptoms include a wide range of subjective and objective conditions like cramping, pain, diarrhea, and bloating ('912 Patent, col. 2:41-42, col. 2:65-68). This could support a broad definition encompassing any level of symptom amelioration.
      • Evidence for a Narrower Interpretation: The specification heavily emphasizes achieving "adequate relief" and a "durability of response" ('912 Patent, col. 2:41-48). A party could argue that "treating" in the context of this invention requires not just temporary symptom reduction but achieving the specific, durable clinical endpoint described throughout the patent.

  • The Term: "rifaximin δ" (or "polymorph δ")

    • Context and Importance: This term is central to claims in the polymorph patent family (e.g., '763 Patent, Claim 1). Infringement of these composition and method claims depends entirely on whether the accused product contains this specific crystalline form of rifaximin. Practitioners may focus on this term because its definition is not a matter of plain English but of precise, technical, physical properties.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: A party might argue that the term covers any rifaximin product that exhibits the most characteristic peaks mentioned in a claim, even if other, minor peaks differ slightly, suggesting substantial similarity is sufficient. The claims use "about" to qualify the peak locations (e.g., "about 5.7°±0.2"), which inherently builds in some flexibility ('763 Patent, col. 9:9-12).
      • Evidence for a Narrower Interpretation: The specification provides a specific powder X-ray diffractogram (FIG. 1) and a list of characteristic 2θ angle values that define the polymorph ('763 Patent, col. 6:23-27). A party will likely argue that "rifaximin δ" is strictly defined by this set of peaks and that any deviation places an accused product outside the claim scope.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement for all asserted patents. The factual basis for this allegation is that Defendant's commercial manufacture, sale, and promotion of the ANDA Product, including its product labeling and instructions, will encourage and instruct physicians and patients to use the generic drug in an infringing manner (Compl. ¶¶ 50-51, 62-63).
  • Willful Infringement: The complaint alleges that Defendant had knowledge of the patents-in-suit, as demonstrated by its reference to them in the Paragraph IV Notice Letter and their listing in the FDA's Orange Book (Compl. ¶¶ 55, 67, 79, 91, 103, 115, 127). The complaint asserts that Defendant's infringement is willful and seeks a declaration that the case is "exceptional" under 35 U.S.C. § 285 (Compl. ¶42; Prayer for Relief ¶ vi).

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

  • A central factual issue will be one of structural identity: Does the crystalline form of rifaximin in Defendant's ANDA product meet the specific X-ray powder diffraction peak limitations defining the patented polymorphs, or does it utilize a different, non-infringing form?
  • A key legal question will be one of induced infringement scope: Will Defendant's proposed product labeling, by seeking a general indication for the treatment of IBS-D in adults, be found to specifically encourage infringement of method claims directed to a narrower patient subpopulation (i.e., "female subjects"), or will Defendant's labeling be deemed not to contain an affirmative instruction to perform the patented method?