DCT

1:17-cv-00762

Kowa Co Ltd v. Hetero Drugs Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-00762, D. Del., 06/14/2017
  • Venue Allegations: Venue is alleged based on Defendants transacting business and selling generic drugs in Delaware, and because the filing of an Abbreviated New Drug Application (ANDA) is a tortious act with foreseeable consequences in the state.
  • Core Dispute: Plaintiffs allege that Defendants' filing of an ANDA to market generic pitavastatin calcium tablets constitutes an act of infringement of a patent claiming specific crystalline forms of that compound.
  • Technical Context: The technology concerns polymorphism in active pharmaceutical ingredients, specifically identifying and claiming novel, stable crystalline forms of pitavastatin calcium, a drug used to treat high cholesterol.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act, triggered by a notice letter dated April 27, 2017, in which Hetero notified Plaintiffs of its ANDA filing (No. 205977) with a Paragraph IV certification, asserting non-infringement of the patent-in-suit.

Case Timeline

Date Event
2003-02-12 U.S. Patent No. 8,557,993 Priority Date
2009-08-03 FDA issues approval letter for Plaintiffs' Livalo® drug (NDA No. 22-363)
2013-10-15 U.S. Patent No. 8,557,993 Issues
2017-04-27 Date of Hetero's Notice Letter regarding its ANDA filing
2017-06-14 Complaint Filing Date

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

U.S. Patent No. 8,557,993 - "Crystalline Forms of Pitavastatin Calcium"

Issued: October 15, 2013. (Compl. ¶16).

The Invention Explained

  • Problem Addressed: The patent addresses the phenomenon of polymorphism, where a single chemical compound can exist in multiple different crystal structures. These different forms can have distinct physical properties, such as solubility and melting point, which in turn "can appreciably influence pharmaceutical properties such as dissolution rate and bioavailability." (’993 Patent, col. 2:5-13). The patent notes the importance of identifying and controlling these forms to ensure a drug product is stable and performs consistently. (’993 Patent, col. 2:13-19).
  • The Patented Solution: The invention claims to have "surprisingly found novel crystalline forms of Pitavastatin calcium," which are designated as Forms A, B, C, D, E, and F, as well as an amorphous form. (’993 Patent, col. 2:19-22). The patent describes processes for preparing these specific forms and characterizes them using analytical techniques, primarily X-ray powder diffraction (XRPD), which produces a unique fingerprint for each crystalline structure. (’993 Patent, Abstract; col. 1:57-65).
  • Technical Importance: The discovery of new, stable polymorphs of a drug substance provides formulation scientists with a larger "repertoire of materials" to design a dosage form with a targeted release profile or other desired characteristics, such as long-term stability. (’993 Patent, col. 2:16-19).

Key Claims at a Glance

  • The complaint alleges infringement of "at least one claim" without specifying which ones. (Compl. ¶29). The first independent claim is Claim 1.
  • Independent Claim 1 is a Markush claim covering several distinct materials. Its essential elements are:
    • A composition of matter which is one of: a crystalline polymorph A, B, C, D, E, F, or the amorphous form, of (3R,5S)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxy-6(E)-heptenoic acid hemicalcium salt.
    • Wherein each polymorph (A-F) is defined by a "characteristic X-ray powder diffraction pattern with characteristic peaks expressed in 2θ" at a specific list of angles and relative intensities (e.g., "polymorph A exhibits a characteristic X-ray powder diffraction pattern with characteristic peaks expressed in 2θ at 5.0 (s), 6.8 (s), 9.1 (s)...").
  • The complaint does not explicitly reserve the right to assert dependent claims, but the "at least one claim" language implicitly does so.

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are Defendants' proposed "1 mg, 2 mg, and 4 mg tablets comprising pitavastatin calcium," for which they seek FDA approval via ANDA No. 205977. (Compl. ¶¶ 9, 22).

Functionality and Market Context

The complaint alleges that Hetero's product is a generic drug intended to be a substitute for Plaintiffs' branded Livalo® product. (Compl. ¶24). Livalo® is approved as an adjunctive therapy to diet to reduce elevated cholesterol and triglycerides. (Compl. ¶13). The complaint asserts that Hetero's product is "bioequivalent" to Livalo®. (Compl. ¶23). The key technical functionality at issue is the specific solid-state form of the pitavastatin calcium active pharmaceutical ingredient (API) contained within the accused tablets.

IV. Analysis of Infringement Allegations

The complaint does not provide a claim chart or sufficient technical detail to construct one. The infringement theory is based on the statutory act of infringement created by 35 U.S.C. § 271(e)(2)(A), which makes the submission of an ANDA seeking approval to market a patented drug an act of infringement. (Compl. ¶28). The complaint alleges on "information and belief" that the pitavastatin drug product described in Hetero's ANDA will, upon commercialization, infringe at least one claim of the ’993 patent. (Compl. ¶29). The core, unstated assumption is that the pitavastatin calcium API in Hetero's product is necessarily one of the crystalline or amorphous forms claimed in the ’993 patent.

No probative visual evidence provided in complaint.

Identified Points of Contention

  • Technical Question: The central factual question for the litigation will be: what is the actual crystalline or amorphous form of the pitavastatin calcium in the product described in Hetero's ANDA? The complaint offers no evidence on this point, and the case will depend on what is revealed in discovery through analysis of Hetero's ANDA samples.
  • Scope Questions: Should discovery reveal a form that is similar but not identical to a claimed form, the case may turn on claim construction. This raises the question of how much variance is allowed by the claim language. For example, does the accused product's XRPD pattern contain the "characteristic peaks" of a claimed polymorph, and how closely must the measured peak positions match the values recited in the claim?

V. Key Claim Terms for Construction

Term: "a characteristic X-ray powder diffraction pattern with characteristic peaks expressed in 2θ at..."

  • Context and Importance: This phrase is the primary means of defining the patented polymorphs. Infringement will depend on whether the accused product's XRPD pattern meets this limitation. Practitioners may focus on this term because the number of required peaks, their exact positions, and their relative intensities are common areas of dispute in pharmaceutical patent litigation.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification states that "2θ angles are recorded with an experimental error of ±0.1-0.2°," which may support an argument that the claimed peak values are not absolute and should encompass a range. (’993 Patent, col. 14:62-63).
    • Evidence for a Narrower Interpretation: The patent claims and describes multiple distinct polymorphs (A-F), each with its own specific list of peaks and corresponding figures (FIGS. 1-6). This may support an argument that the lists are fingerprints intended to be read precisely to distinguish the patented forms from each other and from any other potential forms.

Term: "hemicalcium salt"

  • Context and Importance: This term defines the stoichiometry of the claimed compound. Practitioners may focus on this term because it implies a specific 2:1 ratio of the pitavastatin anion to the calcium cation. Infringement could be avoided if the accused product uses a different salt form or a non-stoichiometric mixture.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: A party might argue that the term should be understood by a person of skill in the art to include materials that are substantially a hemicalcium salt, even with minor impurities or deviations from a perfect 2:1 ratio.
    • Evidence for a Narrower Interpretation: The chemical name is precise, and the patent includes a structural formula depicting two pitavastatin anions associated with one Ca2+ ion, which strongly suggests a strict 2:1 stoichiometric requirement. (’993 Patent, col. 1:30-41).

VI. Other Allegations

Indirect Infringement

The complaint alleges inducement of infringement. (Compl. ¶29). The factual basis is the filing of the ANDA itself, which seeks approval to market the generic product for the same therapeutic uses as the patented Livalo® product. (Compl. ¶¶ 23-24). The allegation implies that Hetero's product labeling will inevitably instruct physicians and patients to administer the tablets, thereby causing an infringing use.

Willful Infringement

The complaint does not contain an explicit allegation of willful infringement. However, it does allege that Hetero provided a "Notice Letter" dated April 27, 2017, which establishes that Hetero had pre-suit knowledge of the ’993 patent. (Compl. ¶25). This fact could later be used to support a claim for willfulness or a request for attorneys' fees under 35 U.S.C. § 285, which is included in the prayer for relief. (Compl. Prayer for Relief ¶(d)).

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

This Hatch-Waxman case appears poised to turn on two central questions, one evidentiary and one of claim scope:

  1. A dispositive evidentiary question will be one of physical characterization: What is the actual solid-state form of the pitavastatin calcium active ingredient in Hetero’s proposed generic product? The answer, to be determined through discovery and expert testing, will be the primary driver of the infringement outcome.

  2. Should the accused product possess a form similar but not identical to a claimed polymorph, a core issue will be one of definitional scope: Can the claim term "characteristic peaks," when read in light of the specification's allowance for experimental error, be construed to cover an XRPD pattern with minor deviations from the explicitly recited peak positions and intensities, or do such deviations define a distinct, non-infringing form?