DCT

1:15-cv-01495

Kowa Co Ltd v. Lupin Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:15-cv-01495, D. Md., 05/22/2015
  • Venue Allegations: Venue is alleged based on Defendants' business transactions in Maryland and the expectation that the filing of an Abbreviated New Drug Application (ANDA) would have tortious consequences within the state.
  • Core Dispute: Plaintiffs allege that Defendants' filing of an ANDA for generic pitavastatin calcium tablets constitutes an act of infringement of a patent covering specific crystalline forms of that drug.
  • Technical Context: The technology concerns pharmaceutical polymorphism, where a single chemical compound can exist in multiple crystalline structures, each with potentially different physical and therapeutic properties.
  • Key Procedural History: This is a Hatch-Waxman action triggered by Defendants' submission of an ANDA to the FDA seeking approval to market a generic drug prior to patent expiration. The complaint notes that Defendants sent Plaintiffs a Notice Letter with a Paragraph IV certification, asserting that the patent-in-suit is not infringed and/or is invalid.

Case Timeline

Date Event
2003-02-12 ’993 Patent Priority Date
2009-08-03 FDA approval for Plaintiffs' Livalo® drug product
2013-10-15 U.S. Patent No. 8,557,993 issues
2015-04-08 Defendants send Notice Letter to Plaintiffs
2015-05-22 Complaint for patent infringement filed

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

U.S. Patent No. 8,557,993 - "Crystalline Forms of Pitavastatin Calcium", issued October 15, 2013

The Invention Explained

  • Problem Addressed: The patent describes the phenomenon of polymorphism, noting that a single drug substance can exist in different crystalline structures (polymorphs) or an amorphous form, each possessing distinct physical properties like melting point and solubility (’993 Patent, col. 2:2-8). These differences can "appreciably influence pharmaceutical properties such as dissolution rate and bioavailability," making it important for drug development to identify and characterize new, stable forms of a drug (’993 Patent, col. 2:8-14).
  • The Patented Solution: The invention claims to have discovered and characterized six new crystalline polymorphs of pitavastatin calcium, designated Forms A, B, C, D, E, and F, as well as a stable amorphous form (’993 Patent, Abstract; col. 2:20-27). Each form is primarily defined by a unique X-ray powder diffraction (XRPD) pattern, which serves as a structural "fingerprint" (’993 Patent, col. 2:28-34; Tables 1-6). The patent also discloses processes for preparing these specific forms.
  • Technical Importance: The discovery of multiple stable polymorphs provides formulation scientists with a "repertoire of materials" to design a pharmaceutical dosage form with desired characteristics, such as consistent manufacturing, shelf-life, and release profile (’993 Patent, col. 2:15-19).

Key Claims at a Glance

  • The complaint asserts infringement of "at least one claim" without specifying which ones (Compl. ¶26). Independent claim 1 is the broadest composition of matter claim.
  • The essential elements of independent claim 1 are:
    • 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) "exhibits a characteristic X-ray powder diffraction pattern with characteristic peaks" defined by a specific list of 2-theta angles and relative intensities.
  • The complaint does not explicitly reserve the right to assert dependent claims, though standard practice suggests this is intended.

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are the 1 mg, 2 mg, and 4 mg tablets comprising pitavastatin calcium for which Lupin Limited and Lupin Pharmaceuticals, Inc. seek FDA approval under Abbreviated New Drug Application ("ANDA") No. 20-6029 (Compl. ¶19).

Functionality and Market Context

  • The proposed product is a generic version of Plaintiffs' Livalo® drug, which is used as an adjunctive therapy to diet to reduce elevated cholesterol levels (Compl. ¶¶10, 21). The complaint alleges that by filing its ANDA, Lupin has indicated its product is bioequivalent to Livalo® and that it seeks approval to commercially manufacture and sell this generic equivalent prior to the expiration of the ’993 Patent (Compl. ¶¶20-21).

IV. Analysis of Infringement Allegations

The complaint does not provide a claim chart or detailed technical allegations mapping elements of the accused product to the patent claims. The infringement allegation is statutory, based on the act of filing the ANDA. The complaint alleges that the filing of ANDA No. 20-6029 for a generic pitavastatin calcium product, for the purpose of obtaining approval to market it before the expiration of the ’993 Patent, constitutes an act of infringement under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶25). It further alleges that the commercial manufacture, use, or sale of the product upon approval will directly infringe or induce infringement of "at least one claim" of the patent (Compl. ¶26). The central, unstated premise is that Lupin's proposed product necessarily contains one of the patented crystalline or amorphous forms of pitavastatin calcium.

No probative visual evidence provided in complaint.

  • Identified Points of Contention:
    • Technical Question: The dispositive factual question will be: What is the solid-state form of the pitavastatin calcium active pharmaceutical ingredient (API) in Lupin's ANDA product? The outcome will likely depend on scientific evidence, such as a comparison of the XRPD pattern of Lupin's API against the patterns claimed for Forms A-F and the amorphous form in the ’993 Patent.
    • Scope Questions: A dispute may arise regarding the meaning of "characteristic peaks" as recited in the claims. The parties may contest how closely an accused product's XRPD pattern must match the claimed peak locations (2-theta angles) and relative intensities to be considered infringing, and whether the absence of certain minor peaks or slight shifts due to experimental conditions is sufficient to avoid infringement.

V. Key Claim Terms for Construction

The complaint does not identify any terms for construction. However, based on the technology, the following term from independent claim 1 is likely to be critical.

  • The Term: "characteristic X-ray powder diffraction pattern with characteristic peaks expressed in 2θ at..."
  • Context and Importance: This phrase is the primary limitation defining the patented polymorphs. Its construction will determine the standard of proof for infringement. Practitioners may focus on this term because the entire infringement analysis hinges on whether Lupin's product exhibits a "characteristic" pattern as claimed, or if experimental variances place it outside the claim's scope.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification discloses that "Small changes in the experimental details can cause small deviation in the d-values and 2θ of characteristic peaks in the X-ray powder diffraction patterns," which may support an interpretation that does not require an exact match (’993 Patent, col. 6:49-52).
    • Evidence for a Narrower Interpretation: The claims provide lengthy, specific lists of 2-theta angles and corresponding relative intensities (e.g., "(s)", "(m)", "(vw)") for each polymorph (’993 Patent, col. 10:52-col. 11:34). A party could argue these detailed "fingerprints" narrowly define the invention and that any significant deviation from the full, recited pattern is non-infringing.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Lupin's future commercial activities will induce infringement of the ’993 Patent (Compl. ¶26). The factual basis for intent is Lupin's filing of the ANDA, which signals its intent to "engage in the commercial manufacture, importation, use, offer for sale, and/or sale" of the accused product upon FDA approval (Compl. ¶20).
  • Willful Infringement: The complaint does not contain an explicit allegation of willful infringement. However, it pleads facts that would support a finding of post-filing willfulness by establishing that Lupin had actual knowledge of the ’993 Patent, at the latest, upon sending its Notice Letter dated April 8, 2015 (Compl. ¶22). The prayer for relief requests attorneys' fees under 35 U.S.C. § 285 but not enhanced damages for willfulness.

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

  • A central issue will be one of factual identification: Does the pitavastatin calcium API in Lupin's ANDA product exist in a crystalline or amorphous form that generates an X-ray powder diffraction pattern matching one of the specific forms defined in the claims of the ’993 patent? This question will be resolved primarily through competing expert analysis of scientific data.
  • The case may also turn on a question of definitional precision: During claim construction, how will the court define the scope of a "characteristic... pattern"? The decision on whether the claims require a near-identical match to the recited peak lists or permit a degree of experimental variation will be critical to the infringement analysis.
  • Finally, Lupin's Notice Letter foreshadows a challenge to the patent's validity (Compl. ¶24). This raises an underlying question for the litigation: Are the claimed polymorphs novel and non-obvious over prior art forms of pitavastatin calcium, or can they be invalidated?