DCT

1:17-cv-05135

Mitsubishi Tanabe Pharma Corp v. Prinston Pharmaceutical Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-05135, D.N.J., 07/13/2017
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey because the defendants maintain regular and established places of business in the state, have committed acts of patent infringement by filing Abbreviated New Drug Applications (ANDAs) directed to the district, and/or have purposefully availed themselves of the jurisdiction through continuous business contacts.
  • Core Dispute: Plaintiffs allege that Defendants' filing of ANDAs to market generic versions of the diabetes drugs INVOKANA® and INVOKAMET® constitutes an act of patent infringement under the Hatch-Waxman Act, as the generic products allegedly contain the specific crystalline form of the active ingredient canagliflozin claimed in the patents-in-suit.
  • Technical Context: The technology concerns a specific crystalline hemihydrate form of canagliflozin, an inhibitor of the sodium-dependent glucose transporter 2 (SGLT2) used to treat type 2 diabetes mellitus.
  • Key Procedural History: The action arises from Defendants' submission of three separate ANDAs (Nos. 210514, 210502, and 210477) to the U.S. Food and Drug Administration (FDA). The patents-in-suit are listed in the FDA's "Orange Book" for the brand-name drugs INVOKANA® and INVOKAMET®. Defendants' notification letters accompanying their ANDA filings assert that the patents are invalid and/or not infringed.

Case Timeline

Date Event
2006-12-04 Priority Date for U.S. Patent Nos. 7,943,582 and 8,513,202
2011-05-17 U.S. Patent No. 7,943,582 Issued
2013-08-20 U.S. Patent No. 8,513,202 Issued
2017-05-30 Date of Prinston's ANDA Notification Letter to Plaintiffs
2017-06-02 Date of DRL's ANDA Notification Letter to Plaintiffs
2017-06-02 Date of Hetero's ANDA Notification Letter to Plaintiffs
2017-07-13 Complaint Filed

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

U.S. Patent No. 7,943,582 - Crystalline form of 1-(β-D-glucopyransoyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene hemihydrate

Issued May 17, 2011

The Invention Explained

  • Problem Addressed: The patent specification describes difficulties in obtaining the active pharmaceutical ingredient, canagliflozin, in a stable and pure crystalline form suitable for commercial manufacturing and pharmaceutical formulation ('582 Patent, col. 1:50-2:1). An amorphous or unstable form can present significant challenges related to handling, purity, and long-term stability ('582 Patent, col. 1:56-62).
  • The Patented Solution: The inventors discovered that canagliflozin could be crystallized from a water-containing solvent to produce a novel and stable crystalline hemihydrate—a crystal structure incorporating one molecule of water for every two molecules of the active compound ('582 Patent, Abstract; col. 2:5-11). This specific solid-state form is described as having favorable handling qualities, making it suitable for large-scale production and formulation into a final drug product ('582 Patent, col. 1:12-16).
  • Technical Importance: The creation of a stable, reproducible crystalline form of an active pharmaceutical ingredient is a critical step in drug development, enabling consistent manufacturing, reliable dosing, and predictable long-term stability ('582 Patent, col. 2:1-4).

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claims 6 and 7 (Compl. ¶¶ 101, 106, 116).
  • Claim 1:
    • A crystalline form of 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene hemihydrate.

U.S. Patent No. 8,513,202 - Crystalline form of 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene hemihydrate

Issued August 20, 2013

The Invention Explained

  • Problem Addressed: As a continuation of the application leading to the '582 patent, the '202 Patent addresses the same technical challenge: the need for a form of canagliflozin with good handling qualities, purity, and stability required for commercial pharmaceutical use ('202 Patent, col. 1:55-2:7).
  • The Patented Solution: The invention is the same crystalline hemihydrate form of canagliflozin, characterized by specific physical properties that distinguish it from amorphous or other potential solid-state forms ('202 Patent, Abstract; col. 2:20-24). The detailed description explains that this form can be produced from a solution containing the compound and water ('202 Patent, col. 2:10-13).
  • Technical Importance: This patent further protects the commercially viable crystalline form of canagliflozin, reinforcing its importance for consistent, large-scale pharmaceutical manufacturing ('202 Patent, col. 2:5-7).

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claims 3-5 (Compl. ¶¶ 111, 121).
  • Claim 1:
    • A crystalline form of 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene hemihydrate.

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are the generic drug products for which the Defendants seek FDA approval via their respective ANDAs: Prinston ANDA No. 210514, DRL ANDA No. 210502, and Hetero ANDA No. 210477 (Compl. ¶1).

Functionality and Market Context

The complaint alleges that the Defendants' ANDA products are generic versions of Plaintiffs' INVOKANA® (canagliflozin) and INVOKAMET® (canagliflozin and metformin hydrochloride) drug products (Compl. ¶¶ 84, 90, 95). These drugs are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (Compl. ¶¶ 19-20). The legal basis for the infringement claim is the statutory act of filing an ANDA to obtain approval for commercialization prior to the expiration of the patents-in-suit (Compl. ¶1).

IV. Analysis of Infringement Allegations

The complaint does not provide claim charts or specific evidence from the Defendants' ANDAs to support its infringement allegations, as is common at the pleading stage of a Hatch-Waxman action. The core infringement theory is that the Defendants' ANDAs seek approval for drug products that contain the specific crystalline hemihydrate form of canagliflozin claimed in the patents.

’582 Patent Infringement Allegations

Plaintiffs allege that each Defendant's filing of an ANDA for a generic canagliflozin product is a technical act of infringement under 35 U.S.C. § 271(e)(2) (Compl. ¶¶ 100, 105, 115). The complaint asserts, upon information and belief, that future discovery and testing will confirm that the active pharmaceutical ingredient in the Defendants' generic products is the same crystalline hemihydrate form claimed in the ’582 Patent (Compl. ¶¶ 101, 106, 116). The patent itself characterizes this claimed form with specific analytical data, including an X-ray powder diffraction (XRD) pattern shown in the patent's Figure 1, which plots diffraction intensity against the angle 2θ ('582 Patent, p. 38, Fig. 1). Proving infringement will likely involve comparing the XRD pattern of the accused generic products to the pattern disclosed and claimed in the patent.

’202 Patent Infringement Allegations

The infringement allegations against DRL and Hetero regarding the ’202 Patent follow the same logic (Compl. ¶¶ 110, 120). Plaintiffs contend that the filing of the ANDAs is an act of infringement and that the generic products described therein will be shown to contain the active ingredient in the crystalline hemihydrate form claimed by the ’202 Patent (Compl. ¶¶ 111, 121). As a continuation, the ’202 Patent uses the same characterization data as the ’582 Patent, including the representative XRD pattern in its Figure 1, to define the claimed crystalline structure ('202 Patent, p. 50, Fig. 1). The dispute will center on whether the generic products fall within the scope of these claims.

Identified Points of Contention

  • Factual Identity: A primary point of contention will be whether the active ingredient in the Defendants' proposed generic products is, in fact, the specific crystalline hemihydrate form claimed in the patents. This will likely be resolved through a battle of experts analyzing competing sets of analytical data (e.g., XRD, thermogravimetric analysis, infrared spectroscopy) for the accused products.
  • Claim Scope: The parties may dispute the scope of the claims. For example, a question may arise as to how much variation from the disclosed characterization data is permissible before a product is considered non-infringing.
  • Validity: The Defendants' notification letters assert that the patents are invalid (Compl. ¶86). This suggests a central part of the defense will be arguments that the claims are anticipated or rendered obvious by prior art relating to canagliflozin or general knowledge of crystallization techniques in the pharmaceutical field.

V. Key Claim Terms for Construction

The Term: "crystalline form"

Context and Importance

This term is at the heart of the invention. The patents do not claim the canagliflozin molecule itself, but rather a specific solid-state arrangement of those molecules. The outcome of the case will depend heavily on whether the Defendants' products embody this claimed "crystalline form."

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: A party seeking a broader view might argue the term covers any crystalline structure of canagliflozin hemihydrate that is not amorphous, unless explicitly disclaimed.
  • Evidence for a Narrower Interpretation: The specification provides highly specific characterization data, such as the XRD pattern in Figure 1 and a list of 2θ values in dependent claim 2 of the '582 patent ('582 Patent, col. 7:30-35). A party seeking a narrower construction will argue that "crystalline form" is implicitly defined by and limited to a structure exhibiting these precise characteristics.

The Term: "hemihydrate"

Context and Importance

This term specifies the stoichiometry of water within the crystal lattice (0.5 moles of water per mole of canagliflozin). To infringe, the accused products must possess this characteristic.

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: A party might argue that "hemihydrate" is a general descriptor and does not require a perfectly exact 0.5:1 ratio, allowing for some deviation due to experimental conditions or measurement error.
  • Evidence for a Narrower Interpretation: The specification provides analytical data supporting the hemihydrate designation, stating the theoretical water content is 1.98% and that thermogravimetric analysis shows a mass loss of 1.705% ('582 Patent, col. 3:19-24). A party will likely argue that this data defines the required water content for a product to be considered a "hemihydrate" under the claims.

VI. Other Allegations

Indirect Infringement

The complaint alleges that if Defendants' ANDAs are approved, their commercial manufacture and sale of the generic products would induce infringement by doctors, pharmacists, and patients, and contribute to infringement by providing the material component for the infringing use (Compl. ¶¶ 101, 106, 111, 116, 121). The alleged basis for inducement is the product labeling that would instruct on the administration of the infringing crystalline form.

Willful Infringement

While the complaint does not use the term "willful," it lays the factual groundwork for such a claim by alleging knowledge. The complaint alleges that the ANDA-filing defendants had knowledge of the patents at least as of the date they submitted their ANDAs (Compl. ¶¶ 102, 107, 112, 117, 122). For other related defendant entities, knowledge is alleged as of the date of service of the complaint (Compl. ¶¶ 117, 122). These allegations of pre-suit and post-suit knowledge could be used to support a later claim for enhanced damages.

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

  • A central issue will be one of factual identity: Does the active pharmaceutical ingredient in the generic products described in the Defendants' ANDAs possess the specific physical and chemical characteristics of the "crystalline form" of canagliflozin "hemihydrate" as claimed in the patents? The resolution will depend on expert testimony and the interpretation of competing analytical data.
  • A key legal question will be one of patent validity: Can the Defendants demonstrate by clear and convincing evidence that the claims are invalid as either anticipated or obvious? This will likely focus on whether the specific crystalline hemihydrate form was disclosed in the prior art or would have been an obvious-to-try variant for a person of ordinary skill in the art seeking to crystallize canagliflozin.