DCT

1:20-cv-01105

Intercept Pharma Inc v. Apotex Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:20-cv-01105, D. Del., 03/04/2021
  • Venue Allegations: Venue is alleged to be proper in Delaware because Defendant Apotex Corp. is a Delaware corporation, and Defendant Apotex Inc., a Canadian corporation, may be sued in any judicial district. Plaintiffs also allege both defendants have continuous and systematic contacts with Delaware and have engaged in prior patent litigation in the district.
  • Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) for a generic version of the drug OCALIVA® (obeticholic acid) constitutes an act of infringement of six U.S. patents covering the compound, its preparation, specific crystalline forms, and pharmaceutical compositions.
  • Technical Context: The dispute centers on obeticholic acid, a synthetic bile acid that functions as an agonist for the Farnesoid X receptor (FXR) and is used in the treatment of chronic liver diseases such as primary biliary cholangitis (PBC).
  • Key Procedural History: This patent infringement action was initiated under the Hatch-Waxman Act following a series of Paragraph IV certification notice letters sent by Apotex to Intercept, beginning in July 2020, asserting that the patents-in-suit are invalid, unenforceable, or will not be infringed by its proposed generic product. The complaint alleges that U.S. Patent No. RE48,286 is a reissue of U.S. Patent No. 7,138,390, and that Defendants had pre-suit knowledge of the original patent.

Case Timeline

Date Event
2001-03-12 U.S. Patent No. RE48,286 Priority Date
2012-06-19 U.S. Patent Nos. 9,238,673, 10,047,117, and 10,174,073 Priority Date
2015-04-27 U.S. Patent Nos. 10,052,337 and 10,758,549 Priority Date
2016-01-19 U.S. Patent No. 9,238,673 Issue Date
2016-05-27 Plaintiff's OCALIVA® New Drug Application (NDA) Approved
2018-08-14 U.S. Patent No. 10,047,117 Issue Date
2018-08-21 U.S. Patent No. 10,052,337 Issue Date
2019-01-08 U.S. Patent No. 10,174,073 Issue Date
2020-07-10 Defendant sends First Notice Letter to Plaintiff
2020-09-01 U.S. Patent No. 10,758,549 Issue Date
2020-10-22 Defendant sends Second Notice Letter to Plaintiff
2020-10-27 U.S. Reissue Patent No. RE48,286 Issue Date
2021-01-27 Defendant sends Third Notice Letter to Plaintiff
2021-03-04 Second Amended Complaint Filing Date

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

U.S. Reissue Patent No. RE48,286 - "Steroids as Agonists for FXR"

  • Issued: October 27, 2020

The Invention Explained

  • Problem Addressed: The patent addresses the role of the Farnesoid X Receptor (FXR), a nuclear receptor involved in bile acid and cholesterol homeostasis, noting that dysregulation of this pathway is associated with cardiovascular and cholestatic liver diseases (RE48,286 Patent, col. 1:11-30). The implicit technical problem is the need for potent and selective compounds that can modulate FXR activity for therapeutic purposes.
  • The Patented Solution: The invention provides a class of 6-alkyl substituted bile acid derivatives that act as FXR agonists (RE48,286 Patent, col. 2:48-51). The core of the invention is the specific chemical structure of these compounds, including obeticholic acid, which is 6-ethyl-chenodeoxycholic acid, claimed to effectively activate the FXR receptor (RE48,286 Patent, Abstract; col. 2:5-10).
  • Technical Importance: This technology provided a new class of synthetic bile acids with potent FXR agonist activity, offering a therapeutic pathway for managing liver and metabolic diseases linked to bile acid regulation (RE48,286 Patent, col. 1:11-15).

Key Claims at a Glance

  • The complaint alleges infringement of one or more unspecified claims (Compl. ¶55). Independent claim 1 is representative of the patent's composition of matter scope.
  • Claim 1 of the RE48,286 Patent claims:
    • A compound of formula (I)
    • Wherein R is ethyl
    • Or a pharmaceutically acceptable salt, solvate, or amino acid conjugate thereof
  • The complaint reserves the right to assert additional claims (Compl. ¶55).

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

  • Issued: January 19, 2016

The Invention Explained

  • Problem Addressed: The patent addresses the need for an efficient, scalable, and high-purity process for manufacturing obeticholic acid for pharmaceutical use (see, e.g., ’117 Patent, col. 32:1-12, a related patent from the same family).
  • The Patented Solution: The invention discloses a multi-step synthesis process for preparing obeticholic acid. A key aspect of the patented solution is the isolation of a novel crystalline intermediate, designated "Form C," which facilitates purification and ultimately leads to a higher purity final product, referred to as non-crystalline "Form 1" (’117 Patent, col. 29:33-44; col. 54:8-14). The process allows for the production of substantially pure obeticholic acid on a large, commercial scale (’117 Patent, col. 32:1-12).
  • Technical Importance: This process provides a commercially viable method for producing a therapeutically important compound with the high level of purity required for a pharmaceutical active ingredient (’117 Patent, col. 6:40-44).

Key Claims at a Glance

  • The complaint alleges infringement of one or more unspecified claims (Compl. ¶71). Independent claim 1 is representative of the patent’s process scope.
  • Claim 1 of the ’673 Patent 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
    • Converting the crystalline obeticholic acid to obeticholic acid Form 1
  • The complaint reserves the right to assert additional claims (Compl. ¶71).

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

  • Issued: August 14, 2018
  • Technology Synopsis: This patent, part of the same family as the ’673 patent, claims specific polymorphic forms of obeticholic acid itself. It describes a non-crystalline form ("Form 1") and a crystalline hydrate ("Form C"), addressing the need for well-characterized and stable solid forms of the drug for pharmaceutical development (’117 Patent, col. 1:11-16, col. 2:35-44).
  • Asserted Claims: One or more unspecified claims (Compl. ¶87).
  • Accused Features: The Apotex ANDA Products, which are tablets containing obeticholic acid (Compl. ¶36, 86).

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

  • Issued: August 21, 2018
  • Technology Synopsis: This patent describes pharmaceutical compositions containing obeticholic acid where the active ingredient has a specific particle size distribution. The invention addresses the technical challenge of ensuring adequate dissolution and bioavailability for a poorly water-soluble drug like obeticholic acid (’337 Patent, Abstract).
  • Asserted Claims: One or more unspecified claims (Compl. ¶103).
  • Accused Features: The Apotex ANDA Products, which are pharmaceutical tablet formulations of obeticholic acid (Compl. ¶36, 102).

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

  • Issued: January 8, 2019
  • Technology Synopsis: This patent, also in the same family as the ’673 and ’117 patents, claims additional specific processes for preparing obeticholic acid. It provides alternative multi-step syntheses, further protecting the manufacturing methods for the drug (’073 Patent, col. 2:1-17).
  • Asserted Claims: One or more unspecified claims (Compl. ¶119).
  • Accused Features: The commercial manufacture of the Apotex ANDA Products (Compl. ¶120).

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

  • Issued: September 1, 2020
  • Technology Synopsis: This patent is related to the ’337 patent and further covers pharmaceutical compositions containing obeticholic acid, including specific formulations and methods of use for treating conditions like primary biliary cholangitis. It builds on the compositions defined by particle size to protect the final drug product (’549 Patent, Abstract).
  • Asserted Claims: One or more unspecified claims (Compl. ¶135).
  • Accused Features: The Apotex ANDA Products, which are tablet formulations of obeticholic acid (Compl. ¶36, 134).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are the "Apotex ANDA Products," which are generic obeticholic acid tablets in 5 mg and 10 mg strengths, as described in Apotex's Abbreviated New Drug Application (ANDA) No. 214862 submitted to the FDA (Compl. ¶1, 11, 36).

Functionality and Market Context

  • The Apotex ANDA Products are purported generic versions of Intercept's OCALIVA® drug product (Compl. ¶36). OCALIVA®'s active ingredient, obeticholic acid, is used for the treatment of primary biliary cholangitis (PBC) (Compl. ¶27). The complaint alleges that Apotex seeks FDA approval to commercially manufacture, use, and sell these generic products in the United States prior to the expiration of the patents-in-suit, with the intent to displace sales of OCALIVA® (Compl. ¶1, 19, 37).
  • No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide detailed, element-by-element infringement allegations or reference any claim chart exhibits. The infringement theory is statutory, based on Defendants' submission of ANDA No. 214862 with a Paragraph IV certification, which constitutes an act of infringement under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶53, 69).

  • RE48,286 Patent Infringement Allegations: The complaint alleges that by filing an ANDA seeking approval to market generic obeticholic acid tablets, Defendants have infringed the ’RE286 Patent, which claims the obeticholic acid compound (Compl. ¶53). Upon FDA approval, the manufacture, use, offer for sale, or sale of the Apotex ANDA Products would constitute direct infringement of the patent (Compl. ¶54). The core allegation is that the active ingredient in the Apotex product is the same chemical compound claimed in the patent.

  • ’673 Patent Infringement Allegations: The complaint alleges that Defendants infringed the ’673 patent by submitting the ANDA for a product that would be made using a patented process (Compl. ¶69). The complaint alleges on information and belief that the future commercial manufacture of the Apotex ANDA Products would infringe one or more claims of the ’673 patent, which covers processes for preparing obeticholic acid (Compl. ¶72).

  • Identified Points of Contention:

    • Scope Questions: For the composition of matter patents (e.g., RE48,286), the primary dispute may not be over infringement scope but over validity, as Apotex’s Paragraph IV letters assert the patents are invalid and/or unenforceable (Compl. ¶38, 44). The question for the court will be whether the claimed subject matter was novel and non-obvious at the time of invention.
    • Technical Questions: For the process patents (e.g., ’673), a central evidentiary question will be whether Apotex’s confidential manufacturing process, as detailed in its ANDA, actually practices the steps recited in the asserted claims. The complaint does not provide factual detail on Apotex's process, raising the question of what evidence will be developed during discovery to support the infringement allegations.

V. Key Claim Terms for Construction

The complaint does not provide sufficient detail for analysis of specific claim terms that may be in dispute. However, based on the technology, certain terms are central to the scope of the asserted patents.

  • The Term: "crystalline obeticholic acid" (from a representative claim of the ’673 patent family).
  • Context and Importance: This term is critical because the ’673 and related patents rely on the formation of a specific crystalline intermediate ("Form C") as a key step for purifying obeticholic acid. Practitioners may focus on this term because if Apotex’s process avoids creating this specific crystalline form, it may have a basis to argue non-infringement of the process claims.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification could be argued to support a broader meaning covering any crystalline form of the acid that arises during synthesis, if not explicitly limited.
    • Evidence for a Narrower Interpretation: The specification of the related ’117 patent provides a precise definition, stating that "crystalline obeticholic acid Form C [is] characterized by an X-ray diffraction pattern including characteristic peaks at about 4.2, 6.4, 9.5, 12.5, and 16.7 degrees 2-Theta" (’117 Patent, col. 2:36-41). This explicit definition with XRPD data may support a narrow construction limited to this specific polymorph.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement for each asserted patent. The basis for inducement is the allegation that Defendants will knowingly and intentionally include a product label and insert with the Apotex ANDA Products containing instructions for administration, thereby encouraging and instructing physicians, health care professionals, and end users to perform acts that directly infringe the patents (Compl. ¶55, 71, 87, 103, 119, 135).
  • Willful Infringement: The complaint alleges that Defendants’ conduct renders the case "exceptional" under 35 U.S.C. § 285, which is the statutory basis for an award of attorneys' fees, often associated with a finding of willfulness. The allegations are based on Defendants’ alleged actual knowledge of the patents-in-suit prior to filing the Apotex ANDA and filing the ANDA "without a reasonable basis" for their non-infringement, invalidity, and/or unenforceability positions (Compl. ¶57, 73, 89, 105, 121, 137). For the ’RE286 Patent, knowledge is specifically alleged based on its predecessor, the ’390 patent (Compl. ¶57).

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

  • A core issue will be one of validity: Can Apotex present clear and convincing evidence to invalidate the asserted claims across six patents covering the obeticholic acid compound, its specific solid forms and formulations, and its methods of manufacture and use? The Paragraph IV certification letters suggest this will be a primary defense strategy.
  • A key evidentiary question will be one of process infringement: Will discovery into Apotex's confidential ANDA reveal that its commercial manufacturing process for generic obeticholic acid necessarily practices the specific synthesis steps recited in the ’673 and ’073 patents, particularly the use of a crystalline intermediate for purification?
  • A final question will be one of enforceability and patent term: Given the reissue patent (RE286) and the complex patent portfolio, the case may raise questions regarding prosecution history, potential disclaimers, and the effective expiration dates of the various patents protecting OCALIVA®, which will determine the potential market entry date for a generic competitor.