DCT
1:23-cv-00714
Intercept Pharmaceuticals, Inc. v. Zenara Pharma Private Limited
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Intercept Pharmaceuticals, Inc. (Delaware) and Intercept Pharma Europe Ltd. (United Kingdom)
- Defendant: Zenara Pharma Private Limited (India)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP; Covington & Burling LLP
- Case Identification: 1:23-cv-00714, D. Del., 06/30/2023
- Venue Allegations: Venue is alleged to be proper because the Defendant is a foreign corporation that may be sued in any judicial district. The complaint also alleges Defendant has purposefully availed itself of the privilege of doing business in Delaware, intends to sell its products there, and has not contested venue in prior litigation in the district.
- Core Dispute: Plaintiff alleges that Defendant’s 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.
- Technical Context: The technology concerns novel steroid compounds that act as agonists for the Farnesoid X receptor (FXR), a key regulator of bile acid and cholesterol metabolism, for the treatment of liver diseases.
- Key Procedural History: This action was filed under 35 U.S.C. § 271(e)(2) following Plaintiff's receipt of a Paragraph IV certification notice letter from Defendant. The patent-in-suit is a reissue of U.S. Patent No. 7,138,390 and has received a five-year patent term extension. The complaint notes Defendant’s Paragraph IV certification alleges the patent is invalid, unenforceable, and/or will not be infringed.
Case Timeline
| Date | Event |
|---|---|
| 2001-03-12 | 'RE286 Patent Priority Date |
| 2006-11-21 | Original U.S. Patent No. 7,138,390 Issued |
| 2016-05-27 | FDA Approves NDA for OCALIVA® |
| 2020-10-27 | U.S. Reissue Patent No. RE48,286 Issued |
| 2023-06-20 | Defendant Mails Paragraph IV Notice Letter to Plaintiff |
| 2023-06-30 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Reissue Patent No. RE48,286 - Steroids as Agonists for FXR
The Invention Explained
- Problem Addressed: The patent addresses the need for therapeutic compounds that can modulate the Farnesoid X Receptor (FXR), which plays a central role in the homeostasis of bile acids and cholesterol (RE48,286 Patent, col. 5:11-18). The patent notes that while naturally-occurring bile acids activate FXR, there was an ongoing search for specific, potent ligands suitable for therapeutic use in managing liver and cardiovascular diseases (RE48,286 Patent, col. 5:38-44).
- The Patented Solution: The invention provides a class of modified bile acid derivatives, specifically compounds of "formula (I)," that are potent FXR agonists (RE48,286 Patent, Abstract). The key structural modification described is the addition of an ethyl group at a specific position (6-alpha) on the steroid core, creating the compound known as obeticholic acid, which selectively activates FXR (RE48,286 Patent, col. 5:36-37, col. 10:46-56).
- Technical Importance: By providing a potent and selective synthetic agonist for FXR, the invention offered a targeted mechanism for therapeutic intervention in pathways controlling lipid metabolism, leading to treatments for cholestatic liver diseases (RE48,286 Patent, col. 5:55-61).
Key Claims at a Glance
- The complaint alleges infringement of "one or more claims" of the patent without specifying them (Compl. ¶35). Independent claim 1 is the broadest compound claim.
- The essential elements of independent claim 1 are:
- A compound of formula (I)
- wherein R is ethyl
- and pharmaceutically acceptable salts, solvates or amino acid conjugates thereof
III. The Accused Instrumentality
Product Identification
- Defendant’s proposed generic obeticholic acid tablets (5 mg and 10 mg), as described in its Abbreviated New Drug Application (ANDA) No. 214855 (Compl. ¶¶1, 22).
Functionality and Market Context
- The accused products are intended to be generic versions of Plaintiff's OCALIVA® drug product (Compl. ¶22). The active pharmaceutical ingredient (API) is obeticholic acid, which functions as an FXR agonist for the treatment of primary biliary cholangitis (PBC) (Compl. ¶¶18, 22).
- The complaint alleges that Defendant’s purpose in filing the ANDA is to commercially manufacture and market its generic product prior to the expiration of the ’RE286 Patent, which would displace sales of OCALIVA® (Compl. ¶¶14, 23).
IV. Analysis of Infringement Allegations
The complaint alleges infringement under 35 U.S.C. § 271(e)(2)(A), where the filing of an ANDA for a drug claimed in a patent is a statutory act of infringement. The analysis focuses on whether the drug product described in the ANDA, if marketed, would infringe.
No probative visual evidence provided in complaint.
'RE286 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 alleged to be obeticholic acid tablets. Obeticholic acid is the chemical compound corresponding to formula (I) where R is ethyl. | ¶22 | col. 11:1-16 |
| and pharmaceutically acceptable salts, solvates or amino acid conjugates thereof. | The ANDA product is a pharmaceutical formulation of obeticholic acid for administration to patients. | ¶22 | col. 11:17-19 |
- Identified Points of Contention:
- Scope Questions: As this is an ANDA case involving a compound claim, infringement is often a matter of direct comparison. A potential dispute could arise regarding the term "pharmaceutically acceptable salts, solvates or amino acid conjugates thereof." The question for the court may be whether the specific crystalline form, salt, or solvate used in Defendant's ANDA product falls within the scope of this language as construed in light of the patent's specification.
- Technical Questions: The primary technical question, central to the infringement analysis, is whether the API specified in Defendant’s confidential ANDA submission is chemically identical to the claimed compound of formula (I). While the complaint alleges it is obeticholic acid (Compl. ¶22), the definitive evidence resides in the ANDA itself, which is not yet part of the public record.
V. Key Claim Terms for Construction
- The Term: "pharmaceutically acceptable salts, solvates or amino acid conjugates thereof"
- Context and Importance: The construction of this term is critical because it defines the boundary of protected formulations beyond the base compound. Practitioners may focus on this term because a potential non-infringement defense in a chemical case is to argue that the accused product utilizes a specific form (e.g., a novel polymorph or salt) that falls outside the claim's scope.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification provides a non-exclusive list of examples, stating the term will "include, for example, basic salts such as metallic salts made from aluminium, calcium, lithium, magnesium, potassium, sodium, and zinc or organic salts..." (’RE286 Patent, col. 6:22-29). The use of "for example" and "such as" may support a broad interpretation covering any salt or solvate suitable for pharmaceutical use.
- Evidence for a Narrower Interpretation: A party could argue that the scope should be limited by the types of salts and solvates exemplified in the patent. The specification also defines a "solvate" as a crystal form containing the compound and a "stoichiometric or a non-stoichiometric amount of a solvent," listing water, methanol, ethanol, or acetic acid as examples (’RE286 Patent, col. 6:38-43). An argument could be made that this constrains the term to conventional forms rather than all possible crystalline structures.
VI. Other Allegations
- Indirect Infringement: The complaint alleges induced infringement under 35 U.S.C. § 271(b). The factual basis is the allegation that Defendant will knowingly and intentionally include a product label and insert with its ANDA products that will contain instructions for administration, thereby encouraging and instructing physicians and patients to perform acts of direct infringement (Compl. ¶35).
- Willful Infringement: The complaint alleges Defendant had "actual knowledge of the RE286 Patent prior to filing the Zenara ANDA" and that its certification of non-infringement or invalidity was made "without a reasonable basis" (Compl. ¶37). This conduct is alleged to render the case "exceptional" under 35 U.S.C. § 285, which could entitle Plaintiffs to attorneys' fees (Compl. ¶37).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue for the court will be patent validity. Defendant’s Paragraph IV certification asserts that the ’RE286 Patent is invalid and/or unenforceable (Compl. ¶24). The case will likely depend on whether Defendant can prove, by clear and convincing evidence, that the asserted claims are invalid, for instance, on grounds of obviousness over prior art chemical compounds or methods.
- A second key question will be one of infringement scope. Assuming the patent is valid, the focus will shift to whether the specific chemical composition and formulation detailed in Defendant's confidential ANDA falls within the literal scope of the asserted claims. This may involve a nuanced analysis of the term "pharmaceutically acceptable salts, solvates or amino acid conjugates thereof" to determine if Defendant's specific formulation is covered.