DCT

1:22-cv-01215

Intercept Pharma Inc v. Zenara Pharma Pvt Ltd

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:22-cv-01215, D. Del., 09/16/2022
  • Venue Allegations: Venue is alleged to be proper as Defendant is a foreign corporation that may be sued in any judicial district and because it intends to market and sell its generic products in Delaware upon FDA approval.
  • Core Dispute: Plaintiffs allege that Defendant's submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of the drug OCALIVA® constitutes an act of infringement of six U.S. patents related to obeticholic acid compositions, preparations, and methods of use.
  • Technical Context: The technology pertains to pharmaceutical forms and manufacturing processes for obeticholic acid, an agonist for the farnesoid X receptor (FXR) used in the treatment of primary biliary cholangitis (PBC), a chronic liver disease.
  • Key Procedural History: The action was initiated under the Hatch-Waxman Act following Defendant's submission of ANDA No. 214855. The lawsuit was filed within the 45-day statutory window after Plaintiffs received a Notice Letter, dated August 6, 2022, in which Defendant provided a Paragraph IV certification alleging that the patents-in-suit are invalid, unenforceable, and/or will not be infringed by its proposed generic product.

Case Timeline

Date Event
2012-06-19 Priority Date for ’673, ’117, and ’073 Patents
2015-04-27 Priority Date for ’337, ’349, and ’549 Patents
2016-01-19 U.S. Patent No. 9,238,673 Issues
2016-05-27 FDA Approves OCALIVA® New Drug Application
2018-08-14 U.S. Patent No. 10,047,117 Issues
2018-08-21 U.S. Patent No. 10,052,337 Issues
2019-01-08 U.S. Patent No. 10,174,073 Issues
2020-08-25 U.S. Patent No. 10,751,349 Issues
2020-09-01 U.S. Patent No. 10,758,549 Issues
2022-08-06 Defendant Mails Paragraph IV Notice Letter to Plaintiffs
2022-09-16 Complaint for Patent Infringement Filed

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

No probative visual evidence provided in complaint.

U.S. Patent No. 9,238,673 - Preparations and Uses of Obeticholic Acid

The Invention Explained

  • Problem Addressed: The patent family addresses the technical challenge of developing a scalable, high-purity manufacturing process for obeticholic acid suitable for a pharmaceutical product, which requires consistent, well-characterized material forms. (’117 Patent, col. 29:1-33).
  • The Patented Solution: The invention describes a process for preparing a non-crystalline form of obeticholic acid, termed "Form 1," which is suitable as a final active pharmaceutical ingredient. A key aspect of the patented process is the use and conversion of a novel crystalline intermediate ("Form C") to achieve high purity in the final non-crystalline product. (’117 Patent, col. 9:8-13, col. 19:6-10).
  • Technical Importance: Establishing a robust manufacturing process that proceeds through a purifiable crystalline intermediate to a defined final form is critical for ensuring the safety, efficacy, and consistency of a commercial drug product. (’117 Patent, col. 6:40-44).

Key Claims at a Glance

  • The complaint alleges infringement of one or more claims without specifying which claims will be asserted (Compl. ¶41). Independent claim 2 is representative of the process claims:
    • A process for preparing obeticholic acid Form 1, comprising the steps of:
    • reacting 3α-hydroxy-6α-ethyl-7-keto-5β-cholan-24-oic acid with NaBH₄ to form crystalline obeticholic acid; and
    • converting crystalline obeticholic acid to obeticholic acid Form 1.
  • The complaint reserves the right to assert other claims, which may include dependent claims (Compl. ¶41).

U.S. Patent No. 10,047,117 - Preparation and Uses of Obeticholic Acid

The Invention Explained

  • Problem Addressed: The patent background describes the difficulty in identifying and producing a stable, reproducible crystalline form (polymorph) of obeticholic acid. Prior efforts reportedly resulted in unsuitable mixed hydrates/solvates or forms that required toxic solvents for preparation, rendering them unsuitable for pharmaceutical development. (’117 Patent, col. 29:1-33).
  • The Patented Solution: The invention discloses a specific, novel crystalline polymorph of obeticholic acid, designated "Form C." This form is defined by a unique set of characteristic peaks in its X-ray powder diffraction (XRPD) pattern and a distinct endotherm value in a Differential Scanning Calorimetry (DSC) thermogram, which allows it to be reliably identified and used as a stable synthetic intermediate. (’117 Patent, col. 1:35-43; ’117 Patent, Fig. 5).
  • Technical Importance: The identification of a stable, characterizable crystalline form provides a critical intermediate that can be isolated and purified at scale, enabling a robust and reproducible manufacturing process for the final drug substance. (’117 Patent, col. 29:34-44).

Key Claims at a Glance

  • The complaint alleges infringement of one or more claims without specification (Compl. ¶57). Independent claim 1 is representative of the composition claims:
    • A crystalline obeticholic acid Form C characterized by an X-ray diffraction pattern including characteristic peaks at:
    • about 4.2,
    • about 6.4,
    • about 9.5,
    • about 12.5, and
    • about 16.7 degrees 2-Theta.
  • The complaint reserves the right to assert other claims, which may include dependent claims (Compl. ¶57).

U.S. Patent No. 10,052,337 - Compositions of Obeticholic Acid and Methods of Use

  • Technology Synopsis: This patent relates to pharmaceutical compositions of obeticholic acid formulated to have specific particle size distributions. The disclosed invention aims to improve properties such as dissolution and stability by controlling the particle size of the active pharmaceutical ingredient. (’337 Patent, Abstract).
  • Asserted Claims: The complaint asserts infringement of "one or more claims" of the ’337 Patent (Compl. ¶73). Independent claim 1 is directed to a pharmaceutical composition comprising obeticholic acid where at least 50% of the particles have a diameter of 200 µm or less.
  • Accused Features: The accused features are the obeticholic acid tablets described in Defendant's ANDA No. 214855, which allegedly have the claimed particle size characteristics (Compl. ¶¶ 71-72).

U.S. Patent No. 10,174,073 - Preparations and Uses of Obeticholic Acid

  • Technology Synopsis: This patent is part of the same family as the ’673 and ’117 patents and is directed to the process for preparing obeticholic acid. The claims focus on specific steps and conditions within the overall manufacturing synthesis, such as the reaction of intermediate compounds with particular reagents under defined temperature and pressure conditions. (’073 Patent, col. 2:1-17).
  • Asserted Claims: The complaint asserts infringement of "one or more claims" of the ’073 Patent (Compl. ¶89). Independent claim 1 is a process claim detailing multiple steps in the synthesis of obeticholic acid Form 1.
  • Accused Features: The infringement allegation is based on the process that Defendant will use to manufacture the generic obeticholic acid tablets described in its ANDA (Compl. ¶¶ 87-88).

U.S. Patent No. 10,751,349 - Compositions of Obeticholic Acid and Methods of Use

  • Technology Synopsis: This patent, related to the ’337 patent, covers pharmaceutical compositions of obeticholic acid with specific excipients and a low alcohol content. The invention is aimed at creating stable formulations for treating conditions like primary biliary cirrhosis. (’349 Patent, Abstract).
  • Asserted Claims: The complaint asserts infringement of "one or more claims" of the ’349 Patent (Compl. ¶105). Independent claim 1 is directed to a method of treating primary biliary cirrhosis with a composition comprising obeticholic acid and a pharmaceutically acceptable excipient having a total alcohol content of less than about 6% (w/w).
  • Accused Features: The accused features are the obeticholic acid tablets described in Defendant's ANDA No. 214855 and the intended use of those tablets to treat PBC (Compl. ¶¶ 103-104).

U.S. Patent No. 10,758,549 - Compositions of Obeticholic Acid and Methods of Use

  • Technology Synopsis: This patent is also part of the ’337 patent family and is directed to methods of treating liver diseases. It claims methods of treatment using obeticholic acid compositions that include both intra-granular and extra-granular portions, a formulation strategy used in tablet manufacturing. (’549 Patent, col. 3:42-50).
  • Asserted Claims: The complaint asserts infringement of "one or more claims" of the ’549 Patent (Compl. ¶121). Independent claim 1 is directed to a method of treating primary biliary cirrhosis using a tablet comprising an intra-granular portion and an extra-granular portion.
  • Accused Features: The accused features are the tablets described in Defendant's ANDA and their intended method of use for treating PBC (Compl. ¶¶ 119-120).

III. The Accused Instrumentality

  • Product Identification: The accused products are the 5 mg and 10 mg obeticholic acid tablets for which Defendant Zenara seeks FDA approval via Abbreviated New Drug Application (ANDA) No. 214855 (Compl. ¶¶ 1, 28).
  • Functionality and Market Context: The Zenara ANDA Products are a generic version of Plaintiffs’ OCALIVA® drug (Compl. ¶1). OCALIVA® is used for the treatment of primary biliary cholangitis (PBC) (Compl. ¶18). Defendant’s product is intended to be a direct market competitor launched prior to the expiration of the patents-in-suit, thereby displacing sales of OCALIVA® (Compl. ¶14, ¶28). The act of infringement alleged in the complaint is the filing of the ANDA itself under 35 U.S.C. § 271(e)(2)(A), which seeks approval to market this generic product before the patents expire (Compl. ¶39, ¶55).

IV. Analysis of Infringement Allegations

The complaint does not contain a claim chart or provide a detailed, element-by-element analysis of infringement for any specific claim. The allegations are framed under the provisions of the Hatch-Waxman Act, where the submission of an ANDA seeking approval to market a drug before the expiration of a listed patent is a statutory act of infringement (Compl. ¶39, ¶55). The complaint alleges that the Zenara ANDA Products, if commercially manufactured, used, or sold, would infringe one or more claims of each of the patents-in-suit (Compl. ¶40, ¶56). As such, a detailed claim chart summary cannot be constructed from the complaint's allegations alone.

  • Identified Points of Contention:
    • Scope Questions: For composition patents like the ’117, ’337, ’349, and ’549 patents, a central dispute will concern whether the specific formulation detailed in Defendant's ANDA falls within the scope of the claims. This raises questions such as: Does the crystalline form of obeticholic acid in the ANDA product exhibit the XRPD peaks required by the claims of the ’117 patent? Does the particle size distribution in the ANDA product meet the limitations of the ’337 patent claims?
    • Technical Questions: For process patents like the ’673 and ’073 patents, infringement analysis under 35 U.S.C. § 271(g) will depend on the manufacturing process described in the ANDA. This raises the question of whether Defendant's process includes the specific steps claimed, such as the conversion from a crystalline intermediate to a non-crystalline final product, as recited in claims of the ’673 patent.

V. Key Claim Terms for Construction

  • The Term: "crystalline obeticholic acid Form C" (’117 Patent, Claim 1)

  • Context and Importance: The definition of this term is central to the infringement analysis for the ’117 patent. The case will likely turn on whether the material in Defendant's ANDA product constitutes "Form C" as claimed. Practitioners may focus on this term because polymorph patents are often litigated over the precise boundaries of the claimed crystalline structure.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: Claim 1 uses the word "about" before each XRPD peak value (e.g., "about 4.2...degrees 2-Theta"), which may support an interpretation that the claim covers crystalline forms with peaks that are close to, but not exactly at, the recited values (’117 Patent, col. 52:35-39).
    • Evidence for a Narrower Interpretation: The specification provides a detailed characterization of Form C, including a specific XRPD diffractogram (FIG. 5) and a DSC thermogram with an endotherm at "about 98±2° C." (’117 Patent, col. 1:39-43; ’117 Patent, Fig. 5). Parties may argue that these specific disclosures limit the scope of "Form C" to material that substantially matches these exemplary characteristics.

  • The Term: "obeticholic acid Form 1" (’673 Patent, Claim 1)

  • Context and Importance: This term defines the final product of the claimed manufacturing process in the ’673 patent. Determining whether Defendant's process produces "Form 1" is essential for the infringement analysis.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification of the related ’117 patent describes Form 1 as "non-crystalline" (’117 Patent, col. 40:1). This may support a broad construction covering any amorphous or non-crystalline version of obeticholic acid produced by the claimed process.
    • Evidence for a Narrower Interpretation: The specification provides characterization data for Form 1, including a DSC curve showing a glass transition temperature and an XRPD pattern showing an amorphous halo (’117 Patent, FIG. 10, FIG. 40). A party could argue that "Form 1" should be limited to non-crystalline material that exhibits these specific physical properties, rather than encompassing all possible non-crystalline forms.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement on the basis that Defendant will knowingly and intentionally include a product label and insert with its generic product. These materials will allegedly contain instructions for physicians and patients to administer the product in a manner that directly infringes one or more claims of the patents-in-suit (Compl. ¶41, ¶57, ¶73, ¶89, ¶105, ¶121).
  • Willful Infringement: The complaint alleges that Defendant had actual knowledge of each patent-in-suit prior to filing its ANDA, as the patents are listed in the FDA's Orange Book (Compl. ¶20, ¶43). It further alleges that Defendant filed its ANDA without a reasonable basis for asserting non-infringement or invalidity, rendering the case "exceptional" under 35 U.S.C. § 285 (Compl. ¶43, ¶59, ¶75, ¶91, ¶107, ¶123).

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

  • A core issue will be one of definitional scope and claim construction: can Plaintiffs establish a claim scope for "crystalline obeticholic acid Form C" and "obeticholic acid Form 1" that is broad enough to read on the specific material described in Defendant's confidential ANDA, or will the court construe these terms narrowly based on the specific characterization data in the patent specifications?
  • A key evidentiary question will be one of technical comparison: does the product described in Defendant's ANDA—in its crystalline form, particle size, and formulation—in fact fall within the properly construed scope of the asserted claims, or has Defendant successfully designed around the patents by creating a product with different physical or chemical characteristics?
  • A central question for the process patents will be proof of manufacture: can Plaintiffs demonstrate, through discovery into Defendant’s confidential ANDA, that the process used to manufacture the accused product includes the specific chemical reaction and purification steps required by the claims of the ’673 and ’073 patents?