DCT

1:20-cv-01214

Intercept Pharma Inc v. MSN Laboratories Pvt Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:20-cv-01214, D. Del., 12/30/2020
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant MSN Pharmaceuticals, Inc. is a Delaware corporation, and Defendant MSN Laboratories Private Limited is an alien corporation that may be sued in any judicial district.
  • Core Dispute: Plaintiff alleges that Defendant's submission of an Abbreviated New Drug Application (ANDA) to market a generic version of the drug OCALIVA® constitutes an act of patent infringement under the Hatch-Waxman Act, infringing six patents related to the obeticholic acid compound, its crystalline forms, pharmaceutical compositions, and methods of use.
  • Technical Context: The technology concerns obeticholic acid, a modified bile acid that acts as an agonist for the Farnesoid X receptor (FXR), a key regulator of bile acid, lipid, and glucose metabolism primarily in the liver and intestine.
  • Key Procedural History: The asserted U.S. Patent No. RE48,286 is a reissue of U.S. Patent No. 7,138,390, which was originally asserted in the litigation. The complaint alleges that Defendants submitted Paragraph IV certifications to the FDA, asserting that the patents-in-suit are invalid, unenforceable, and/or will not be infringed by the proposed generic product.

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 FDA Approval of OCALIVA® (NDA No. 207999)
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
2020-07-28 Date of First Notice Letter from Defendants
2020-09-01 U.S. Patent No. 10,758,549 Issue Date
2020-10-27 U.S. Patent No. RE48,286 Issue Date
2020-11-18 Date of Second Notice Letter from Defendants
2020-12-30 First Amended Complaint Filing Date

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

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

Issued October 27, 2020

The Invention Explained

  • Problem Addressed: The patent describes the Farnesoid X Receptor (FXR) as a nuclear receptor involved in the homeostasis of cholesterol and bile acids, but notes that its endogenous ligand was not definitively known at the time of invention (RE48286 Patent, col. 1:10-40). This created a need for compounds that could specifically activate FXR for therapeutic purposes.
  • The Patented Solution: The invention provides a class of steroid compounds that act as agonists for FXR (RE48,286 Patent, col. 2:4-6). The core of the invention is the chemical structure of these compounds, including 6α-ethyl-chenodeoxycholic acid (obeticholic acid), which is claimed to activate the FXR pathway (RE48,286 Patent, col. 2:25-30; Abstract).
  • Technical Importance: The development of potent and selective FXR agonists provided a novel therapeutic mechanism for treating cholestatic liver diseases and other metabolic disorders regulated by the FXR pathway (RE48,286 Patent, col. 2:45-52).

Key Claims at a Glance

  • The complaint alleges infringement of one or more claims of the patent without specifying particular claims (Compl. ¶49). Independent claim 1 is representative of the core composition of matter invention.
  • Independent Claim 1:
    • A compound of formula (I) [a chenodeoxycholic acid scaffold]
    • wherein R is ethyl [specifying an ethyl group at the 6-alpha position]
    • or a pharmaceutically acceptable salt, solvate, or amino acid conjugate thereof.

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

Issued January 19, 2016

The Invention Explained

  • Problem Addressed: The development of a pharmaceutical product requires an active ingredient that can be produced reliably and with consistent physical properties. The patent addresses the need for stable, solid forms of obeticholic acid suitable for pharmaceutical formulation and large-scale manufacturing (’673 Patent, col. 29:3-14).
  • The Patented Solution: The invention discloses specific crystalline forms (polymorphs) of obeticholic acid, identified as Form C and Form F, among others ('673 Patent, Abstract). The patent characterizes "Form C" by its unique X-ray powder diffraction (XRPD) pattern, illustrated in Figure 5, and its thermal properties, providing a stable and reproducible solid form of the drug substance ('673 Patent, col. 29:43-48, Fig. 5).
  • Technical Importance: Identifying and characterizing specific crystalline forms of a drug is critical for pharmaceutical development, as different polymorphs can have different solubility, stability, and bioavailability, affecting the drug's safety and efficacy ('673 Patent, col. 28:56-65).

Key Claims at a Glance

  • The complaint alleges infringement of one or more claims of the patent without specifying particular claims (Compl. ¶65). Independent claim 1 is representative of the core crystalline form invention.
  • Independent Claim 1:
    • Crystalline obeticholic acid Form C
    • 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.

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

Issued August 14, 2018

  • Technology Synopsis: This patent relates to processes for preparing obeticholic acid and the resulting product forms. It describes multi-step chemical syntheses and purification methods to produce substantially pure obeticholic acid, including a non-crystalline form designated as Form 1 (’117 Patent, col. 6:41-47, col. 32:33-38).
  • Asserted Claims: The complaint does not specify asserted claims (Compl. ¶81). Claim 12 is a representative independent product claim.
  • Accused Features: The complaint alleges that Defendants' manufacture of their generic obeticholic acid tablets will infringe the patent (Compl. ¶80).

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

Issued August 21, 2018

  • Technology Synopsis: This patent addresses the formulation of obeticholic acid for improved therapeutic properties. The invention claims methods of treating primary biliary cirrhosis (PBC) by administering a composition of obeticholic acid where the active ingredient has a specific particle size distribution, which can affect dissolution and bioavailability (’337 Patent, Abstract, col. 1:57-64).
  • Asserted Claims: The complaint does not specify asserted claims (Compl. ¶97). Claim 1 is a representative independent method claim.
  • Accused Features: The complaint alleges that Defendants' proposed generic product will be used to treat PBC, the same indication as OCALIVA®, thereby infringing the patented method (Compl. ¶¶24, 97).

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

Issued January 8, 2019

  • Technology Synopsis: This patent is directed to pharmaceutical compositions containing a specific non-crystalline form of obeticholic acid, referred to as Form 1. The claims cover formulations comprising this non-crystalline form along with pharmaceutically acceptable excipients (’073 Patent, col. 35:22-30).
  • Asserted Claims: The complaint does not specify asserted claims (Compl. ¶113). Claim 1 is a representative independent composition claim.
  • Accused Features: The complaint alleges that Defendants' ANDA product is a pharmaceutical composition containing obeticholic acid that will infringe the patent (Compl. ¶112).

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

Issued September 1, 2020

  • Technology Synopsis: This patent claims methods of treating various liver diseases, including PBC, by administering a composition of obeticholic acid. The claims cover titration regimens and methods of administering the drug in combination with other agents (’549 Patent, col. 27:28-40, col. 28:24-34).
  • Asserted Claims: The complaint does not specify asserted claims (Compl. ¶129). Claim 1 is a representative independent method claim.
  • Accused Features: The complaint alleges that Defendants' proposed generic product will be marketed with a label instructing its use for the treatment of PBC, thereby infringing the patented methods (Compl. ¶¶24, 129).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is the generic drug product described in Defendant's ANDA No. 215017, seeking FDA approval for obeticholic acid tablets in 5 mg and 10 mg strengths (Compl. ¶¶1, 33).

Functionality and Market Context

  • The ANDA product is a generic version of Plaintiff's OCALIVA® product (Compl. ¶33). It contains the same active pharmaceutical ingredient, obeticholic acid, and is intended to be used for the same medical indication: the treatment of primary biliary cholangitis (PBC) (Compl. ¶¶1, 24). The complaint alleges that Defendants intend to commercially manufacture and sell this product in the United States upon FDA approval, which would directly compete with and displace sales of OCALIVA® (Compl. ¶¶11, 19). The act of submitting the ANDA itself is the statutory basis for infringement under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶1).
  • No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not contain or reference detailed claim charts. The infringement theory is statutory under 35 U.S.C. § 271(e)(2)(A), which defines the submission of an ANDA to obtain approval for a drug claimed in a patent as an act of infringement. The core allegation is that Defendant’s ANDA product is a bioequivalent generic version of OCALIVA® that will contain the claimed compound and be administered according to a label that instructs its use for the claimed methods.

RE48,286 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A compound of formula (I) . . . wherein R is ethyl The ANDA product is an obeticholic acid tablet, and obeticholic acid is the compound claimed. ¶33 col. 11:27-58
or a pharmaceutically acceptable salt, solvate, or amino acid conjugate thereof The ANDA product is a pharmaceutical formulation containing the claimed compound. ¶33 col. 11:59-61

9,238,673 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
Crystalline obeticholic acid Form C The complaint alleges infringement by the submission of an ANDA for obeticholic acid tablets, without specifying the crystalline form. ¶63 col. 29:43-44
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 The complaint does not allege that Defendant's product exhibits these specific peaks; this will be a subject of discovery. ¶63 col. 29:44-48

Identified Points of Contention

  • Scope Questions: For the '673 Patent, a central issue will be one of evidentiary scope: what is the actual crystalline form (polymorph) of the obeticholic acid in MSN's ANDA product? The infringement analysis will depend on whether discovery reveals that MSN’s active pharmaceutical ingredient meets the specific XRPD peak limitations required by the asserted claims.
  • Technical Questions: While direct infringement of the 'RE286 composition of matter patent may be straightforward if MSN's product contains obeticholic acid, the validity of this and the other patents will be a primary point of contention. Questions will arise as to whether the later-patented crystalline forms and methods of use are non-obvious and novel over the original compound disclosure.

V. Key Claim Terms for Construction

  • The Term: "crystalline obeticholic acid Form C" (from '673 Patent, Claim 1)
  • Context and Importance: The definition of this term is dispositive for the infringement analysis of the '673 Patent. The dispute will center on whether the obeticholic acid in MSN’s product constitutes this specific, patented polymorph. Practitioners may focus on this term because polymorph patents grant narrow protection, and infringement requires demonstrating that the accused product contains the specific crystal structure defined in the claims.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The claim defines Form C by a list of five "characteristic peaks at about" specific 2-Theta values ('673 Patent, col. 29:44-48). A party may argue that meeting these five peaks, within a reasonable margin of error connoted by "about," is sufficient to fall within the claim scope, regardless of other peaks or relative intensities.
    • Evidence for a Narrower Interpretation: The specification provides a full XRPD pattern in Figure 5 and states Form C is "characterized by an X-ray diffraction pattern substantially similar to that set forth in FIG. 5" ('673 Patent, col. 2:38-40). A party may argue that the claim should be construed to require not only the presence of the listed peaks but also a substantial similarity to the overall pattern of Figure 5, potentially including the relative intensity of the peaks and the absence of peaks characteristic of other forms.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon FDA approval, Defendants will induce infringement by "knowingly and intentionally includ[ing] a product label and insert containing instructions for administering the MSN ANDA Products" to patients for the patented indications (Compl. ¶¶49, 65, 81, 97, 113, 129).
  • Willful Infringement: Willfulness is alleged based on Defendants' purported actual knowledge of the patents-in-suit prior to filing the ANDA (Compl. ¶¶67, 83, 99, 115, 131). The complaint further alleges that Defendants filed their ANDA "without a reasonable basis for asserting" that the patents were invalid, unenforceable, or not infringed, rendering the case "exceptional" under 35 U.S.C. § 285 (Compl. ¶¶67, 83, 99, 115, 131).

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

  • A core issue will be one of polymorphic scope: does the obeticholic acid in Defendant's ANDA product exist in a specific crystalline form, such as the "Form C" claimed in the '673 Patent, or does it utilize a different polymorph or an amorphous form that falls outside the scope of the asserted claims directed to specific solid-state forms?
  • A second central issue will be patent validity: can Plaintiff's patents covering specific crystalline forms, pharmaceutical compositions, and methods of use withstand Defendant's challenges of obviousness and lack of novelty in light of the prior art, including the original disclosure of the obeticholic acid compound itself?
  • A key evidentiary question will concern induced infringement: assuming the method-of-use claims are valid, will the language of the FDA-approved label for Defendant's generic product instruct users to perform all the steps of the claimed methods, thereby establishing the requisite intent for inducement?