DCT

2:21-cv-19293

Curia IP Holdings LLC v. Salix Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:21-cv-19293, D.N.J., 09/16/2022
  • Venue Allegations: Venue is alleged based on Defendants maintaining a presence, conducting regular business, and deriving substantial revenue in New Jersey. The complaint also notes that certain Defendants have previously submitted to the court’s jurisdiction by filing other actions in the district.
  • Core Dispute: Plaintiff alleges that Defendants’ XIFAXAN® antibiotic, as manufactured since 2015, infringes four patents related to specific polymorphic mixtures of the active ingredient rifaximin.
  • Technical Context: The technology concerns pharmaceutical solid-state chemistry, where the specific crystalline structure (polymorph) of a drug compound can significantly impact its stability, bioavailability, and therapeutic efficacy.
  • Key Procedural History: The complaint preemptively addresses a potential on-sale bar defense by alleging that the accused product ("Later XIFAXAN®") is compositionally different from the version sold before the patents' priority dates ("Early XIFAXAN®") due to manufacturing changes made around 2015. It also alleges that Defendant Alfasigma had knowledge of the patent family as early as 2017 through its opposition to a European counterpart patent.

Case Timeline

Date Event
2004-07-01 Approx. launch of 200 mg "Early XIFAXAN®" product
2010-05-01 Approx. launch of 550 mg "Early XIFAXAN®" product
2013-07-26 Priority Date for '355' Patent
2014-03-31 Priority Date for '915', '415', and '257' Patents
2015-04-23 FDA approval of a Salix manufacturing change for XIFAXAN®
2015-10-15 FDA approval of a Salix manufacturing change for XIFAXAN®
2015-11-17 '355 Patent Issued
2016-06-16 FDA approval of a Salix manufacturing change for XIFAXAN®
2017-01-06 FDA approval of a Salix manufacturing change for XIFAXAN®
2017-11-08 Alfasigma allegedly filed opposition to European counterpart patent
2020-02-11 '915 Patent Issued
2020-08-18 '415 Patent Issued
2021-03-30 '257 Patent Issued
2022-09-16 Amended Complaint Filed

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

U.S. Patent No. 9,186,355 - "Rifaximin Crystalline Forms And Methods Of Preparation Thereof"

The Invention Explained

  • Problem Addressed: Different crystalline forms (polymorphs) of the antibiotic rifaximin exhibit different properties, such as bioavailability, and can inter-convert depending on conditions like humidity. This creates a challenge in manufacturing a drug product with consistent and predictable behavior (Compl. ¶33; ’915 Patent, col. 2:10-24).
  • The Patented Solution: The patent claims a specific composition of rifaximin that is a mixture of two distinct polymorphs, α and β. The invention is defined by specific weight-based ratios of the α and β forms and a specific range of water content, which together are described as providing both a "fast acting portion and a slow acting portion" of the antibiotic (’355 Patent, Abstract & col. 2:50-55).
  • Technical Importance: Achieving a stable and reproducible mixture of polymorphs with a predictable dissolution profile is critical for ensuring consistent therapeutic effect and meeting the strict quality control standards required for pharmaceutical manufacturing (’915 Patent, col. 2:35-41).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claim 1 (Compl. ¶¶78-80).
  • Essential elements of independent claim 1 include:
    • A rifaximin composition comprising mixed crystalline polymorphs rifaximin α and rifaximin β;
    • Containing about 3-12% (w/w) of the rifaximin β crystalline polymorph;
    • Containing from about 2% to about 5% by weight water;
    • Wherein the aqueous dissolution rates of the α and β forms provide a fast acting portion and a slow acting portion of rifaximin antibiotic.
  • The complaint implicitly reserves the right to assert other claims by alleging infringement of "one or more claims" (Compl. ¶78).

U.S. Patent No. 10,556,915 - "Polymorphic Mixture of Rifaximin and its Use for the Preparation of Solid Formulations"

The Invention Explained

  • Problem Addressed: The patent's background section notes that conventional crystallization and drying processes are "critical since they did not consistently afford the desired α or α/β mixtures," often resulting in undesired or unstable polymorphic forms, which undermines manufacturing consistency (’915 Patent, col. 2:18-24).
  • The Patented Solution: The invention is a specific rifaximin polymorphic mixture of the α and β forms, defined by a relative ratio of 85/15±3 and characterized by a unique "fingerprint" of 18 specific peaks in its X-Ray Diffraction (XRD) spectrum. The patent also discloses a detailed manufacturing process designed to reliably produce this specific mixture (’915 Patent, Abstract & col. 4:25-65).
  • Technical Importance: The invention purports to solve a key manufacturing problem by providing a reproducible process to create a stable, well-defined polymorphic mixture, thereby ensuring the "consistency" of the active pharmaceutical ingredient (API) and the final drug product (’915 Patent, col. 2:35-41).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claims 1 and 4 (Compl. ¶¶37, 87-89).
  • Essential elements of independent claim 1 include:
    • A Rifaximin polymorphic mixture of α/β form in a relative ratio of 85/15±3;
    • Characterized by an X-Ray spectrum with 18 specific characteristic 2theta values.
  • Independent claim 4 requires the same mixture and XRD spectrum as claim 1, but adds a process limitation: the mixture must be "produced by drying wet Rifaximin at atmospheric pressure, at a temperature between 38 and 42° C. to reach a final water content of 6±2%."
  • The complaint implicitly reserves the right to assert other claims (Compl. ¶87).

U.S. Patent No. 10,745,415 - "Polymorphic Mixture of Rifaximin and its Use for the Preparation of Solid Formulations"

  • Technology Synopsis: This patent claims a method of treating a patient by administering the specific rifaximin polymorphic mixture that is the subject of the ’915 patent. The invention addresses the treatment of traveler's diarrhea and hepatic encephalopathy by using a pharmaceutical composition containing the α/β polymorphic mixture characterized by the specific 85/15±3 ratio and its corresponding X-Ray spectrum (’415 Patent, Abstract; Compl. ¶38).
  • Asserted Claims: Independent claims 1 (treatment of traveler's diarrhea) and 9 (treatment of hepatic encephalopathy) are asserted (Compl. ¶¶38, 97-99).
  • Accused Features: The accused activity is the administration of the "Later XIFAXAN®" product for its indicated uses, allegedly as instructed by the product's labeling (Compl. ¶97).

U.S. Patent No. 10,961,257 - "Polymorphic Mixture of Rifaximin and its Use for the Preparation of Solid Formulations"

  • Technology Synopsis: This patent claims the same polymorphic mixture of rifaximin described in the ’915 patent, defined by the α/β ratio and the characteristic X-Ray spectrum. The patent addresses the same technical problem of creating a consistent and stable pharmaceutical composition (’257 Patent, Abstract). Claim 11 adds a "product-by-process" limitation identical to that in claim 4 of the ’915 patent.
  • Asserted Claims: Independent claims 1 and 11 are asserted (Compl. ¶¶39, 106-108).
  • Accused Features: The accused feature is the "Later XIFAXAN®" product itself, which allegedly is or contains the rifaximin mixture claimed in the patent (Compl. ¶¶71, 107).

III. The Accused Instrumentality

Product Identification

The accused products are the 200 mg and 550 mg dosage forms of "Later XIFAXAN®" tablets (Compl. ¶69). The complaint defines "Later XIFAXAN®" as the product manufactured and sold on or after manufacturing changes were made in 2015 and subsequent years, distinguishing it from the non-accused "Early XIFAXAN®" sold prior to these changes (Compl. ¶¶51-52).

Functionality and Market Context

XIFAXAN® is an antibiotic used for the treatment of traveler's diarrhea and for reducing the risk of hepatic encephalopathy recurrence (Compl. ¶42). The complaint alleges that one or more manufacturing changes approved by the FDA since 2015 altered the polymorphic character of the rifaximin active ingredient in the XIFAXAN® product (Compl. ¶¶47-49). It is this allegedly altered product, "Later XIFAXAN®," that is accused of containing the patented α/β polymorphic mixture (Compl. ¶¶69, 71).

Visual Evidence in Complaint

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

U.S. Patent No. 9,186,355 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A rifaximin composition comprising mixed crystalline polymorphs rifaximin α and rifaximin β The "Later XIFAXAN®" product allegedly comprises both the α and β polymorphic forms of rifaximin. ¶69 col. 2:50-52
containing about 3-12% (w/w) of the rifaximin β crystalline polymorph... The product allegedly contains α and β polymorphs "in a relative ratio that falls within the scope of the claims." ¶71 col. 2:52-55
and from about 2% to about 5% by weight water... The complaint does not provide a specific allegation regarding the water content of the accused product. N/A col. 2:55-58
wherein the aqueous dissolution rates of the α and β forms provide a fast acting portion and a slow acting portion of rifaximin antibiotic. This functional property is implicitly alleged by accusing the commercial product, but no specific dissolution data is provided. ¶79 col. 2:58-62

U.S. Patent No. 10,556,915 Infringement Allegations

Claim Element (from Independent Claim 1 & 4) Alleged Infringing Functionality Complaint Citation Patent Citation
A Rifaximin polymorphic mixture of α/β form in a relative ratio of 85/15±3... (Claim 1) The "Later XIFAXAN®" product allegedly comprises a mixture of α and β polymorphs in a ratio that falls "within the scope of the claims." ¶71 col. 5:35-36
characterized by an X-Ray spectrum with characteristic 2theta values at... [18 peaks listed] (Claim 1) The complaint makes a conclusory allegation that the mixture in the accused product meets the claimed XRD characteristics, but provides no specific data. ¶¶37, 71 col. 5:36-41
...produced by drying wet Rifaximin at atmospheric pressure, at a temperature between 38 and 42° C. to reach a final water content of 6±2%. (Claim 4) The infringing product is alleged to have resulted from "manufacturing changes," but the complaint does not allege Defendant uses these specific process parameters. ¶¶49, 71 col. 11:4-7

Identified Points of Contention

  • Evidentiary Questions: The complaint alleges that "Later XIFAXAN®" meets the specific compositional and structural limitations of the claims (e.g., the polymorphic ratio, the water content, the XRD peaks) but provides no supporting analytical data. A central point of contention will be whether Plaintiff's testing of the accused product, revealed in discovery, can substantiate these conclusory allegations.
  • Product-by-Process Claims: For claims that recite manufacturing steps (e.g., Claim 4 of the ’915 Patent), Plaintiff bears the burden of proving the accused product was made by the claimed process. The complaint's general allegation of "manufacturing changes" raises the question of whether Plaintiff can obtain evidence of Defendant's proprietary manufacturing methods to prove this element.
  • "Early" vs. "Later" XIFAXAN®: The factual distinction between the pre-2015 and post-2015 versions of XIFAXAN® is foundational to the Plaintiff's case, particularly for overcoming a potential on-sale bar defense. A major dispute will likely surround the evidence proving that the polymorphic character of the drug actually changed as a result of the post-2015 manufacturing modifications and that the earlier product was, in fact, non-infringing.

V. Key Claim Terms for Construction

The Term: "a relative ratio of 85/15±3" (’915 Patent, Claim 1)

  • Context and Importance: This term is the quantitative heart of the composition claim. Its construction will determine how the ratio is measured and what degree of variation is permitted. Practitioners may focus on this term because the ±3% range defines the boundary between infringing and non-infringing compositions.
  • Evidence for a Broader Interpretation: The specification's use of "about" in other contexts and the ±3 tolerance itself suggests that the invention is not limited to an exact ratio, potentially allowing for standard measurement variability or batch-to-batch fluctuations.
  • Evidence for a Narrower Interpretation: The claim recites a specific numerical range. A party could argue that this range is a hard limit and that the method for determining the ratio must be the one disclosed in the patent (e.g., via the XRD calibration curve shown in FIG. 1), which could limit how the ratio is proven (’915 Patent, col. 7:6-14).

The Term: "characterized by an X-Ray spectrum with characteristic 2theta values at..." (’915 Patent, Claim 1)

  • Context and Importance: This term provides the structural "fingerprint" of the claimed mixture. The dispute will concern how closely an accused product's XRD spectrum must match the 18 recited peaks and their corresponding relative intensities.
  • Evidence for a Broader Interpretation: A party may argue that "characterized by" means the listed peaks are the most important identifiers, but that the presence of other minor peaks or slight shifts in position or intensity (due to instrument or sample differences) does not defeat a finding of infringement.
  • Evidence for a Narrower Interpretation: The claim lists not only 18 specific 2theta values but also their parenthetical relative intensities (e.g., "8.80 (100%)"). A defendant could argue that these values are not merely illustrative but are defining limitations that must be met with high fidelity, as taught in the detailed examples (’915 Patent, col. 5:36-41).

VI. Other Allegations

Indirect Infringement

The complaint alleges inducement and contributory infringement of the ’415 method-of-treatment patent. Inducement is predicated on Defendants' product labeling, which allegedly instructs physicians and patients to administer Later XIFAXAN® for the patented therapeutic uses (Compl. ¶¶97, 101). Contributory infringement is based on selling the product with the knowledge that it is especially made for and has no substantial non-infringing use other than the patented methods (Compl. ¶102). The complaint also alleges contributory infringement by Alfasigma for supplying the allegedly infringing rifaximin API to Salix (Compl. ¶¶82, 91, 110).

Willful Infringement

Willfulness is alleged for all four patents based on Defendants' alleged knowledge of the patents on or after their respective issue dates (Compl. ¶¶83, 92, 100, 111). The complaint further supports pre-suit knowledge by alleging that Defendant Alfasigma filed an opposition against a European counterpart patent in 2017, putting it on notice of the patent family (Compl. ¶74).

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

  • A central issue will be one of factual proof: Can the Plaintiff produce dispositive analytical evidence (such as X-Ray diffraction data) to prove that the "Later XIFAXAN®" product, as sold since 2015, actually possesses the specific polymorphic ratios and structural characteristics required by the patent claims? The complaint's allegations are currently conclusory on this point.
  • The case may hinge on a question of invalidity and timing: Will the Defendants be able to demonstrate that the XIFAXAN® product sold before the patents' priority dates ("Early XIFAXAN®") meets the claim limitations, thereby creating an invalidating on-sale bar? The resolution will depend on a factual deep-dive into the product's formulation history and whether the Plaintiff's narrative of a post-2015 compositional change holds up to scrutiny.
  • A key legal battle will be over claim scope: Can the phrase "characterized by an X-Ray spectrum," which defines the invention's structural fingerprint, be construed to allow for minor variations in peak position and intensity, or will the court require a strict, literal match to the 18 values recited in the claims? The answer will determine the effective breadth of the patents.