DCT

1:18-cv-01678

Astellas US LLC v. Wockhardt Bio AG

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:18-cv-01678, D. Del., 10/25/2018
  • Venue Allegations: Venue is alleged to be proper as to Wockhardt USA because it is incorporated in Delaware. Venue is alleged to be proper as to Wockhardt Bio, a non-U.S. resident, on the basis that it may be sued in any judicial district.
  • Core Dispute: Plaintiffs allege that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the cardiac stress agent Lexiscan® (regadenoson) constitutes an act of infringement of two patents covering specific crystalline forms (polymorphs) and manufacturing processes for the drug.
  • Technical Context: The technology concerns pharmaceutical chemistry, specifically the synthesis and isolation of a stable, pure, crystalline form of an active pharmaceutical ingredient, which is critical for ensuring consistent safety, efficacy, and shelf-life in commercial drug products.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' notification to Plaintiffs of their ANDA submission. The complaint notes that U.S. Patent No. 9,085,601 is the subject of a pending reissue proceeding, which may affect the scope or validity of its claims during the litigation.

Case Timeline

Date Event
2006-02-03 Priority Date for ’183 and ’601 Patents
2012-01-31 U.S. Patent No. 8,106,183 Issues
2015-07-21 U.S. Patent No. 9,085,601 Issues
2017-06-19 Wockhardt sends notice letter regarding ANDA filing
2018-10-25 Complaint Filed

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

U.S. Patent No. 8,106,183 - "Process for preparing an A₂ₐ-adenosine receptor agonist and its polymorphs"

Issued January 31, 2012

The Invention Explained

  • Problem Addressed: The patent addresses the need for improved methods to synthesize large quantities of the A₂ₐ-adenosine receptor agonist regadenoson. The background notes that previously known methods utilized protecting groups, a chemical step that is "undesirable for large scale syntheses" because it can add complexity and cost to manufacturing (’183 Patent, col. 1:62-65).
  • The Patented Solution: The invention provides a large-scale synthesis process that avoids protecting groups. It also identifies that the resulting compound can exist in several different crystalline forms, or polymorphs, and discloses a method to isolate a specific, stable monohydrate form (referred to as Form A) (’183 Patent, Abstract; col. 2:2-10). The ability to consistently produce one stable polymorph is a key aspect of the solution.
  • Technical Importance: For a pharmaceutical product, controlling the polymorphic form of the active ingredient is critical for ensuring predictable dissolution rates, bioavailability, and stability, which are essential for regulatory approval and commercial manufacturing.

Key Claims at a Glance

  • The complaint asserts independent claims 1 and 8.
  • Claim 1: A monohydrate of the specific chemical compound (regadenoson) that is in a crystalline form.
  • Claim 8: The crystalline monohydrate of claim 1, which has a specific ¹H NMR spectrum as shown in the patent's FIG. 1.
  • The complaint also asserts dependent claims 2-3 and 9, reserving the right to assert others (Compl. ¶30).

U.S. Patent No. 9,085,601 - "Process for preparing an A₂ₐ-adenosine receptor agonist and its polymorphs"

Issued July 21, 2015

The Invention Explained

  • Problem Addressed: As with the parent '183 Patent, this patent addresses the need for a commercially viable, large-scale synthesis of regadenoson and the isolation of a stable polymorphic form (’601 Patent, col. 1:55-65).
  • The Patented Solution: The invention describes a pharmaceutical composition containing the crystalline monohydrate form of regadenoson. The claims focus on the final drug composition prepared from this specific, stable polymorph, including purity requirements related to the absence of process-related impurities like 2-hydrazinoadenosine (’601 Patent, col. 2:2-10; Claim 2).
  • Technical Importance: The patent claims a final pharmaceutical formulation defined by its starting material (the specific polymorph) and purity profile, protecting not just the active ingredient itself but also the formulated drug product that possesses desirable characteristics derived from the manufacturing process.

Key Claims at a Glance

  • The complaint asserts independent claim 1.
  • Claim 1: A pharmaceutical composition prepared from a crystalline monohydrate form of regadenoson by adding at least one pharmaceutically acceptable carrier.
  • The complaint also asserts dependent claims 2-5, reserving the right to assert others (Compl. ¶35).

III. The Accused Instrumentality

Product Identification

The "Wockhardt ANDA product," identified as a 0.4 mg/5 mL (0.08 mg/mL) intravenous solution of regadenoson (Compl. ¶2).

Functionality and Market Context

The Wockhardt ANDA product is a generic version of Plaintiffs' Lexiscan® drug (Compl. ¶2). It is intended for use as a "pharmacologic stress agent indicated for radionuclide myocardial perfusion imaging (MPI) in patients unable to undergo adequate exercise stress" (Compl. ¶22, ¶26). The complaint alleges that by filing its ANDA, Wockhardt has necessarily represented to the FDA that its product has the same active ingredient, dosage form, strength, and is bioequivalent to Lexiscan (Compl. ¶25).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

The complaint, characteristic of initial ANDA filings, does not provide a detailed, element-by-element infringement analysis or a claim chart. The central allegation is that Wockhardt’s submission of ANDA No. 209187, seeking approval to market its generic regadenoson product before the patents-in-suit expire, constitutes a technical act of infringement under 35 U.S.C. § 271(e)(2) (Compl. ¶30, ¶35). The complaint further alleges that the future commercial manufacture and sale of the Wockhardt ANDA product would infringe under 35 U.S.C. § 271(a), (b), and (c) (Compl. ¶31, ¶36). The complaint does not contain sufficient detail to construct a technical claim chart.

Identified Points of Contention

  • Factual Question: A primary question for discovery will be whether the regadenoson active pharmaceutical ingredient in the Wockhardt ANDA product is, in fact, the specific crystalline monohydrate form claimed in the '183 Patent. The case will likely involve detailed analysis of spectroscopic and diffraction data (e.g., XRPD, NMR) of Wockhardt's product.
  • Scope Question: For the '601 Patent, a question is whether Wockhardt’s final drug product meets the limitations of the product-by-process claims. For example, a dispute may arise over whether Wockhardt's product is "substantially free of 2-hydrazinoadenosine" as required by dependent claim 2, and what level of impurity satisfies that limitation.

V. Key Claim Terms for Construction

  • The Term: "monohydrate ... in a crystalline form" (’183 Patent, Claim 1)
  • Context and Importance: This term is the foundation of the '183 Patent's asserted claims. The infringement analysis will depend entirely on whether Wockhardt's generic product is determined to be this specific polymorph. Practitioners may focus on this term because polymorphic identity is a frequent and critical point of dispute in pharmaceutical patent litigation.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The plain language of claim 1 does not specify a particular crystalline form beyond it being a monohydrate. A plaintiff might argue this covers any crystalline monohydrate of regadenoson.
    • Evidence for a Narrower Interpretation: The specification explicitly describes and characterizes "Form A" as the most stable monohydrate polymorph and provides detailed analytical data, including a specific X-Ray diffraction pattern in FIG. 3 and an NMR spectrum in FIG. 1 (’183 Patent, col. 6:39-47; Claim 2). A defendant may argue that the claims should be construed as being limited to this specifically disclosed and characterized "Form A."

VI. Other Allegations

Indirect Infringement

The complaint alleges that Wockhardt's future commercial activities would constitute inducement of infringement (Compl. ¶31, ¶36). This allegation is likely based on the premise that Wockhardt's product labeling will instruct medical professionals to administer the drug for its approved (and allegedly patented) use, thereby encouraging direct infringement by end-users.

Willful Infringement

The complaint does not contain an explicit allegation of willful infringement. However, it establishes Defendants’ pre-suit knowledge of the patents by referencing the notice letter sent by Wockhardt to the Plaintiffs on June 19, 2017, as required under the Hatch-Waxman Act (Compl. ¶23). This fact could potentially be used to support a later claim for enhanced damages if infringement is found.

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

  • A core issue will be one of polymorphic identity: What is the actual crystalline structure of the regadenoson active ingredient that Wockhardt intends to market? Discovery and expert analysis of Wockhardt’s ANDA samples will be central to determining whether it is the same "crystalline monohydrate" (Form A) disclosed and claimed in the patents-in-suit.
  • A key legal question will be one of claim scope: How will the court construe the term "monohydrate...in a crystalline form" from the '183 Patent? The outcome of the case may hinge on whether the claim is interpreted broadly to cover any crystalline monohydrate of the compound, or narrowly to cover only the specific "Form A" polymorph detailed in the patent's specification.
  • An ancillary question relates to purity: For the '601 Patent, a factual dispute may arise over whether Wockhardt’s final drug product meets the purity limitations of the asserted claims, specifically whether it is "substantially free" of certain process-related impurities.