DCT

1:17-cv-05278

Mitsubishi Tanabe Pharma Corp v. Apotex Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-05278, D.N.J., 07/19/2017
  • Venue Allegations: Plaintiffs allege venue is proper in the District of New Jersey because Defendants are subject to personal jurisdiction in the district, have committed acts of infringement there through the filing of their drug application directed at a New Jersey-based entity, and continuously transact business in the state.
  • Core Dispute: Plaintiffs allege that Defendants’ filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the diabetes drug INVOKANA® constitutes an act of infringement of two patents covering a specific crystalline form of the active ingredient, canagliflozin.
  • Technical Context: The technology relates to pharmaceutical polymorphs, specifically a stable, crystalline hemihydrate form of canagliflozin, an SGLT2 inhibitor for treating type 2 diabetes, which is critical for consistent manufacturing and drug product performance.
  • Key Procedural History: This is a Hatch-Waxman action triggered by Defendants’ submission of ANDA No. 210449 and a related notice letter dated June 5, 2017, asserting that the patents-in-suit are not infringed. Plaintiffs filed this complaint within the 45-day statutory window. The complaint also notes that the same patents are the subject of related litigation against other generic pharmaceutical manufacturers.

Case Timeline

Date Event
2006-12-04 Priority Date for ’582 and ’202 Patents
2011-05-17 U.S. Patent No. 7,943,582 Issued
2013-08-20 U.S. Patent No. 8,513,202 Issued
2017-06-05 Apotex sends notice letter regarding ANDA filing
2017-07-19 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"

  • Patent Identification: 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 (Compl. ¶9).

The Invention Explained

  • Problem Addressed: The patent’s background section notes the general importance for a commercial drug product to possess good handling qualities, purity, and stability, and states that "there have been difficulties in obtaining a crystal form of the compound of formula (I) [canagliflozin] from organic solvents" (’582 Patent, col. 1:36-52). The technical challenge was to develop a form of the drug substance suitable for reliable, large-scale pharmaceutical manufacturing.
  • The Patented Solution: The inventors discovered that canagliflozin could be produced as a specific crystalline "hemihydrate," a form where the crystal lattice incorporates one-half of a water molecule for every molecule of the drug (’582 Patent, Abstract; col. 4:18-23). This specific crystalline form is described as having "good handling qualities and characteristics" and being "reproducible on a commercial scale" (’582 Patent, col. 2:9-12; col. 1:53-57). The patent identifies this novel form by its unique analytical properties, including its X-ray powder diffraction (XRPD) pattern and infra-red (IR) spectrum (’582 Patent, col. 2:13-28).
  • Technical Importance: The creation of a single, stable, and reproducible crystalline polymorph of an active pharmaceutical ingredient is a critical step in drug development, necessary to ensure consistent bioavailability, shelf-life, and quality in the final drug product (’582 Patent, col. 1:36-48).

Key Claims at a Glance

  • The complaint asserts infringement of at least claims 1, 6, and 7, with claim 1 being the sole independent claim asserted (Compl. ¶45).
  • Independent Claim 1 requires:
    • 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-glucopyransoyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene hemihydrate"

  • Patent Identification: U.S. Patent No. 8,513,202, "Crystalline form of 1-(β-D-glucopyransoyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene hemihydrate," issued August 20, 2013 (Compl. ¶12).

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 difficulty in obtaining a stable and pure crystalline form of canagliflozin from organic solvents suitable for commercial production (’202 Patent, col. 1:59-62).
  • The Patented Solution: The invention is the same crystalline hemihydrate form of canagliflozin disclosed in the parent ’582 Patent. This patent further characterizes and claims the specific crystalline form by reference to its distinct analytical data, particularly its infra-red (IR) spectrum (’202 Patent, col. 2:25-39). The stated purpose is to provide a novel material with "good handling qualities and characteristics" for pharmaceutical use (’202 Patent, col. 2:22-24).
  • Technical Importance: This patent provides another way to define and protect the commercially valuable crystalline form of canagliflozin, reinforcing the intellectual property surrounding the specific polymorph used in the INVOKANA® drug product (’202 Patent, col. 1:50-58).

Key Claims at a Glance

  • The complaint asserts infringement of at least claims 1 and 3-5, with claim 1 being the sole independent claim asserted (Compl. ¶50).
  • Independent Claim 1 requires:
    • A crystalline form of 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene hemihydrate;
    • having an infra-red spectrum in mineral oil comprising the following main peaks: 1626, 1600, 1549, and 1507 cm⁻¹.

III. The Accused Instrumentality

Product Identification

The accused instrumentality is the "Apotex Inc ANDA Product" detailed in Abbreviated New Drug Application (ANDA) No. 210449 (Compl. ¶1). This product is intended to be a generic version of Janssen's INVOKANA® (canagliflozin) 100 mg and 300 mg tablets (Compl. ¶40).

Functionality and Market Context

The Apotex ANDA Product is a pharmaceutical tablet containing canagliflozin, an SGLT2 inhibitor. Its intended use, as a generic version of INVOKANA®, is to "improve glycemic control in adults with type 2 diabetes mellitus" (Compl. ¶15). The complaint alleges that Apotex seeks to manufacture and sell this product in the U.S. before the expiration of the patents-in-suit, which is the statutory basis for this Hatch-Waxman litigation (Compl. ¶1, ¶38).

IV. Analysis of Infringement Allegations

The complaint alleges infringement based on the act of filing the ANDA and on the product that would be commercialized if the ANDA is approved. The core technical allegation, made on information and belief, is that the canagliflozin contained within the Apotex ANDA Product is the specific crystalline hemihydrate form claimed in the patents-in-suit. No probative visual evidence provided in complaint.

7,943,582 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A crystalline form of 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene hemihydrate. The complaint alleges, upon information and belief, that discovery and testing will show the Apotex ANDA Product contains canagliflozin in the specific crystalline hemihydrate form. ¶41, ¶45 col. 7:26-29

8,513,202 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A crystalline form of 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene hemihydrate The complaint alleges, upon information and belief, that the Apotex ANDA Product contains canagliflozin in the claimed crystalline hemihydrate form. ¶41, ¶50 col. 8:13-15
having an infra-red spectrum in mineral oil comprising the following main peaks: 1626, 1600, 1549, and 1507 cm⁻¹. The complaint alleges, upon information and belief, that testing will show the Apotex ANDA Product exhibits this specific IR spectrum. ¶41, ¶50 col. 3:10-13

Identified Points of Contention

  • Evidentiary Question: The complaint does not provide any test results or technical data for the Apotex ANDA Product. It premises its infringement allegations on future "discovery/testing" (Compl. ¶41, ¶45). The central point of contention will therefore be factual and evidentiary: does the active ingredient in Apotex's product, when analyzed, actually exhibit the crystalline hemihydrate structure and the specific analytical characteristics (e.g., XRPD, IR data) required by the asserted claims?
  • Scope Question: A potential dispute may arise over the precise scope of the claims. For instance, dependent claims and specification language refer to patterns and spectra being "substantially the same" as those depicted in the patent figures ('582 Patent, col. 2:22-24). The court may need to determine how much, if any, variation from the patent's exemplary data is permissible for an accused product to still fall within the scope of the claims.

V. Key Claim Terms for Construction

  • The Term: "crystalline form of ... hemihydrate"

  • Context and Importance: This term is the foundation of both patents. The dispute will turn on whether Apotex's product is this specific polymorph, as opposed to an amorphous solid or a different crystalline form (e.g., an anhydrate or a different solvate). Plaintiffs' ability to prove that Apotex's product is both "crystalline" and a "hemihydrate" (containing a 0.5:1 molar ratio of water to canagliflozin in its crystal structure) is essential to their infringement case.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The independent claims simply recite the "crystalline form of... hemihydrate" without tying it to specific analytical data, which could support an argument that any product meeting this general structural definition infringes.
    • Evidence for a Narrower Interpretation: The specifications of both patents, along with their dependent claims, define the invention with very high specificity using analytical data. The '582 patent provides specific XRPD peak values (col. 2:19-21) and the '202 patent provides specific IR peak values (col. 8:16-18). A defendant would likely argue that the claims must be construed as limited to a crystalline form that strictly conforms to the detailed analytical data provided in the specification.

  • The Term: "having an infra-red spectrum in mineral oil comprising the following main peaks: 1626, 1600, 1549, and 1507 cm⁻¹" (’202 Patent, Claim 1)

  • Context and Importance: This limitation defines the invention in the '202 Patent by reference to a specific analytical signature. Practitioners will focus on this term because infringement requires a direct match between the IR spectrum of Apotex's product and this list of peaks. Any meaningful deviation could form the basis of a non-infringement defense.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification discloses a form "having substantially the same IR spectrum, as set out in FIG. 2" ('202 Patent, col. 2:37-39), which may suggest that minor, immaterial variations from the exemplary spectrum do not escape the claim's scope.
    • Evidence for a Narrower Interpretation: The claim uses the word "comprising" followed by a precise list of four peak values. A defendant could argue this creates a rigid definition, and that a product lacking any one of these "main peaks," or exhibiting them at slightly different wavenumbers, falls outside the literal scope of the claim.

VI. Other Allegations

  • Indirect Infringement: The complaint includes boilerplate allegations of induced and contributory infringement under 35 U.S.C. §§ 271(b) and (c) (Compl. ¶45, ¶50). These allegations are prospective, based on what would happen if Apotex were to commercially launch its product. The factual basis for inducement would presumably be Apotex's product labeling, which would instruct physicians and patients to use the drug in an infringing manner.
  • Willful Infringement: The complaint alleges that Apotex has had knowledge of the patents since at least the date it submitted its ANDA (Compl. ¶46, ¶51). Furthermore, the complaint establishes pre-suit knowledge by citing the June 5, 2017 notice letter sent by Apotex’s counsel (Compl. ¶38). This alleged knowledge, both pre- and post-suit, could form the basis for a claim of willful infringement and a request for enhanced damages.

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

  • A core issue will be one of empirical evidence: will laboratory analysis of the Apotex ANDA product demonstrate that it contains the specific canagliflozin crystalline hemihydrate claimed in the patents? The case will likely hinge on a battle of experts interpreting analytical data from techniques like X-ray powder diffraction, infra-red spectroscopy, and thermogravimetric analysis.
  • A key legal question will be one of definitional scope: how will the court construe the claims defining the crystalline form? The central issue in claim construction will be determining the permissible degree of variation, if any, from the specific analytical peak values enumerated in the patents, which will set the boundary for what constitutes an infringing product.