DCT

1:18-cv-01675

Astellas US LLC v. Hospira Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:18-cv-01675, D. Del., 07/17/2019
  • Venue Allegations: Venue is alleged to be proper as to Wockhardt USA because it is incorporated in Delaware. Venue is alleged as to Wockhardt Bio on the basis that it is not a resident of the United States and 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 Plaintiffs' Lexiscan® drug product constitutes an act of infringement of three patents related to the active ingredient regadenoson, its crystalline form, and its method of preparation.
  • Technical Context: The technology relates to the pharmaceutical compound regadenoson, a selective agonist used as a pharmacologic stress agent in cardiac perfusion imaging for patients unable to undergo exercise-based stress tests.
  • Key Procedural History: This action is a consolidated case arising under the Hatch-Waxman Act, triggered by Defendants' ANDA filing. The complaint notes that an earlier-asserted patent (U.S. Patent No. 9,085,601) was replaced by its reissue patent, U.S. Patent No. RE 47,301, following a reissue proceeding at the U.S. Patent and Trademark Office. Defendants provided notice letters asserting that the patents-in-suit are invalid, unenforceable, and/or not infringed by their proposed generic product.

Case Timeline

Date Event
2006-02-03 Priority Date for ’183, ’301, and ’883 Patents
2012-01-31 U.S. Patent No. 8,106,183 Issues
2013-09-03 U.S. Patent No. 8,524,883 Issues
2015-07-21 U.S. Patent No. 9,085,601 (predecessor to ’301 Patent) Issues
2017-06-19 Wockhardt notifies Plaintiffs of ANDA filing
2018-10-25 Plaintiffs file original complaint in the consolidated action
2019-03-19 U.S. Reissue Patent No. RE 47,301 Issues
2019-07-10 Wockhardt sends second notice letter regarding the ’301 Patent
2019-07-17 Plaintiffs file First Amended Complaint

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’s background section states that prior methods for synthesizing the active pharmaceutical ingredient regadenoson, while suitable for small-scale lab work, utilized protecting groups, a practice described as "undesirable for large scale syntheses" (’183 Patent, col. 1:64-67).
  • The Patented Solution: The invention provides a large-scale synthesis process for regadenoson that avoids the use of protecting groups, thereby improving efficiency for commercial manufacturing (’183 Patent, col. 2:15-20). Additionally, the patent identifies that the compound can exist in at least three different crystalline forms, or polymorphs, and discloses that the most stable of these is a monohydrate, which is desirable for a final drug product (’183 Patent, col. 2:1-10).
  • Technical Importance: The invention provides a commercially viable method for manufacturing a stable, pure form of a clinically significant cardiac stress agent, which is a critical step in bringing a pharmaceutical product to market (’183 Patent, col. 1:59-62).

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claims 4-9 (Compl. ¶40).
  • Claim 1, an independent claim, recites the following essential elements:
    • A monohydrate of (1-{9-[(4S,2R,3R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-aminopurin-2-yl}pyrazol-4-yl)-N-methylcarboxamide,
    • which monohydrate is in a crystalline form.

U.S. Reissue Patent No. RE 47,301 - “Process for preparing an A2A-adenosine receptor agonist and its polymorphs,” Issued March 19, 2019

The Invention Explained

  • Problem Addressed: Similar to the ’183 patent, this patent addresses the need for convenient methods for producing large quantities of the regadenoson compound in high yield and purity, noting that prior small-scale methods are not commercially ideal (’301 Patent, col. 2:12-20).
  • The Patented Solution: The patent claims a pharmaceutical composition containing the crystalline monohydrate form of regadenoson that is "substantially free" of a specific process impurity, 2-hydrazinoadenosine (’301 Patent, claim 6). This suggests the invention is directed not only to the final product but also to a specific level of purity achieved through the disclosed manufacturing process.
  • Technical Importance: In pharmaceutical manufacturing, controlling for and minimizing specific process-related impurities is critical for drug safety, stability, and regulatory approval, making a claim to a composition defined by its purity level technically and commercially significant (’301 Patent, col. 16:34-40).

Key Claims at a Glance

  • The complaint asserts independent claim 6 and dependent claims 8-9, 11, 13-14, and 16-17 (Compl. ¶45).
  • Claim 6, an independent claim, recites the following essential elements:
    • A pharmaceutical composition prepared from a crystalline monohydrate form of the compound (1-{9-[(4S,2R,3R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-aminopurin-2-yl}pyrazol-4-yl)-N-methylcarboxamide
    • that is substantially free of 2-hydrazinoadenosine;
    • and a pharmaceutically acceptable carrier.

Multi-Patent Capsule

  • Patent Identification: U.S. Patent No. 8,524,883, “Monohydrate of (1-{9-[4S,2R,3R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-aminopu-rin-2-yl}pyrazol-4-yl)-N-methylcarboxamide,” Issued September 3, 2013
  • Technology Synopsis: This patent claims methods of preparing a pharmaceutical composition by combining the stable, crystalline monohydrate form of regadenoson with a carrier, such as a buffered aqueous solution (’883 Patent, col. 2:54-65). The invention focuses on the final formulation of the drug product, ensuring its suitability for administration to patients.
  • Asserted Claims: Claims 1-3 (Compl. ¶53).
  • Accused Features: The complaint alleges on information and belief that Wockhardt uses processes covered by the claims of the ’883 patent to prepare its ANDA product and will import and sell a product made by that process (Compl. ¶32, 53).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality is the "Wockhardt ANDA product," a proposed generic 0.4 mg/5 mL (0.08 mg/mL) intravenous solution of regadenoson (Compl. ¶2).
  • Functionality and Market Context: The product is a generic version of Plaintiffs' Lexiscan® drug, a pharmacological stress agent used in cardiac nuclear stress tests for patients who cannot perform exercise-based tests (Compl. ¶2, 24-25). By filing its ANDA, Wockhardt has represented to the FDA that its product contains the same active ingredient, has the same dosage form and strength, and is bioequivalent to Lexiscan® (Compl. ¶29). Wockhardt seeks approval to market its product for the same indication as Lexiscan® (Compl. ¶30). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The infringement allegations are based on the submission of ANDA No. 209187, which constitutes a technical act of infringement under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶40, 45). The complaint alleges that Wockhardt’s product is a generic version of Lexiscan® and therefore necessarily contains the claimed compound and composition.

’183 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A monohydrate of (1-{9-[(4S,2R,3R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-aminopurin-2-yl}pyrazol-4-yl)-N-methylcarboxamide... The Wockhardt ANDA product is a generic version of Lexiscan® and contains regadenoson, which the ANDA represents is the same active ingredient as the claimed compound. ¶29, 40 col. 1:53-58
...which monohydrate is in a crystalline form. The ANDA product is alleged to be bioequivalent to Lexiscan®, which contains the stable crystalline monohydrate form of the compound. ¶29, 40 col. 2:5-10

’301 Patent Infringement Allegations

Claim Element (from Independent Claim 6) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical composition prepared from a crystalline monohydrate form of the compound... The Wockhardt ANDA product is alleged to be a pharmaceutical composition containing the crystalline monohydrate form of regadenoson. ¶29, 45 col. 2:48-52
...that is substantially free of 2-hydrazinoadenosine; The complaint alleges that the Wockhardt ANDA product infringes this claim, which requires the composition to be substantially free of this specified impurity to meet regulatory standards for a bioequivalent product. ¶45 claim 6
...and a pharmaceutically acceptable carrier. The Wockhardt ANDA product is an intravenous solution, which necessarily includes a pharmaceutically acceptable carrier. ¶2 col. 6:22-26
  • Identified Points of Contention:
    • Scope Questions: A central dispute may arise over the meaning of "substantially free of 2-hydrazinoadenosine" in the ’301 Patent. The parties may contest the specific level of impurity permissible for a product to be considered "substantially free."
    • Technical Questions: A primary evidentiary question will concern the actual manufacturing process detailed in Wockhardt's confidential ANDA. Does that process result in a product that meets all claim limitations, particularly the purity requirements of the ’301 Patent and the process steps of the ’883 Patent? The complaint alleges this on "information and belief," with the definitive evidence to emerge during discovery (Compl. ¶32).

V. Key Claim Terms for Construction

  • The Term: "substantially free of 2-hydrazinoadenosine" (’301 Patent, claim 6)

  • Context and Importance: This term defines a required level of purity for the claimed pharmaceutical composition. Its construction will be critical to the infringement analysis, as the presence of the 2-hydrazinoadenosine impurity above a certain threshold in Wockhardt's product could lead to a finding of non-infringement. Practitioners may focus on this term because negative limitations defining purity are often key points of dispute in pharmaceutical patent litigation.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent does not provide a specific numerical value or percentage for "substantially free." Plaintiffs may argue this implies a standard industry understanding of purity required for regulatory approval, where the impurity is not present in an amount that would affect the product's safety or efficacy.
    • Evidence for a Narrower Interpretation: The patent specification distinguishes the claimed invention from prior art that allegedly resulted in impurities (’301 Patent, col. 4:1-9). Defendants may argue that "substantially free" should be construed to mean a level of purity that is uniquely and necessarily achieved only by the patented process, potentially rendering their own process non-infringing.

  • The Term: "crystalline form" (’183 Patent, claim 1)

  • Context and Importance: This term is essential for defining the solid-state structure of the claimed monohydrate. The patents disclose several different polymorphs (Forms A, B, C) as well as an amorphous material. Whether "crystalline form" is limited to the specifically disclosed and preferred "Form A" or covers any non-amorphous structure could determine the scope of the claim.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The plain meaning of "crystalline" suggests any ordered solid-state structure, as distinguished from the disclosed "Amorphous Material" (’183 Patent, col. 6:66).
    • Evidence for a Narrower Interpretation: The specification repeatedly identifies "Form A" as the most stable polymorph and the desired final product, and provides its specific X-ray powder diffraction data (’183 Patent, col. 6:40-52; FIG. 3). A defendant may argue that the claims, read in light of the specification, should be limited to this specifically characterized and preferred embodiment.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges inducement of and contribution to infringement for all asserted patents (Compl. ¶41-42, 46-47, 53-54). The allegations are based on the assertion that Wockhardt, upon receiving FDA approval, will encourage and instruct medical professionals and patients to use its generic product for the patented indications, thereby inducing infringement.
  • Willful Infringement: The complaint does not contain an explicit allegation of "willful infringement" or a request for enhanced damages under 35 U.S.C. § 284. However, it pleads facts establishing Wockhardt's pre-suit knowledge of the patents via notice letters dated June 19, 2017 and July 10, 2019 (Compl. ¶27, 28).

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

  • A core issue will be one of "validity": As indicated by Defendants' notice letters, the validity of the asserted patents, likely on grounds of obviousness over prior art methods for synthesizing and purifying similar chemical compounds, will be a central battleground in the litigation.
  • A key evidentiary question will be one of "factual correspondence": Does the actual manufacturing process and resulting composition detailed in Wockhardt's confidential ANDA fall within the scope of the asserted claims? This will turn on a comparison of Wockhardt’s proprietary information with the patent claims, particularly the process limitations of the ’883 Patent.
  • The outcome may also hinge on a question of "definitional scope": How will the court construe the term "substantially free of 2-hydrazinoadenosine"? The interpretation of this purity threshold will be dispositive for infringement of a key composition patent, the ’301 Patent.