DCT

1:17-cv-05005

Mitsubishi Tanabe Pharma Corp v. Aurobindo Pharma USA Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-05005, D.N.J., 07/07/2017
  • Venue Allegations: Plaintiffs allege venue is proper in the District of New Jersey based on Defendants' regular and established places of business in the state, their consent to venue in prior litigation, and their intent to market the accused generic products in New Jersey.
  • Core Dispute: Plaintiffs allege that Defendants' submission of Abbreviated New Drug Applications (ANDAs) to the FDA for generic versions of the diabetes drugs INVOKANA® and INVOKAMET® constitutes an act of infringement of two patents covering a specific crystalline form of the active ingredient, canagliflozin.
  • Technical Context: The technology concerns a specific crystalline polymorph (a hemihydrate) of a pharmaceutical compound, which is critical for ensuring drug stability, manufacturability, and consistent bioavailability.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act, triggered by notification letters from the Defendants informing Plaintiffs of their ANDA filings seeking to market generic drugs before the expiration of Plaintiffs' patents, which are listed in the FDA's "Orange Book." The letters from Defendants allegedly assert that their proposed generic products do not infringe the patents-in-suit and/or that the patents are invalid.

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
2017-05-23 InvaGen and Macleods send Paragraph IV notification letters
2017-05-24 Aurobindo sends Paragraph IV notification letter
2017-07-07 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, issued May 17, 2011.

The Invention Explained

  • Problem Addressed: The patent’s background section describes the difficulty in obtaining a stable and pure crystal form of the active pharmaceutical ingredient (API) canagliflozin from organic solvents, which is a prerequisite for reproducible, large-scale manufacturing of a drug product that meets exacting pharmaceutical specifications (ʼ582 Patent, col. 1:47-54).
  • The Patented Solution: The inventors discovered that canagliflozin can be crystallized from a water-containing solvent to produce a novel and stable crystalline hemihydrate form (a crystal structure that incorporates one water molecule for every two molecules of the API) (’582 Patent, col. 2:5-12). This specific crystalline form is described as having favorable handling qualities and stability, making it suitable for commercial pharmaceutical use (’582 Patent, col. 1:55-62).
  • Technical Importance: Achieving a consistent, stable crystalline form of an API is crucial for controlling its therapeutic properties, such as dissolution rate and bioavailability, as well as its shelf-life and manufacturability into final dosage forms like tablets (’582 Patent, col. 1:35-46).

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claims 6 and 7 (Compl. ¶77).
  • Independent Claim 1:
    • A crystalline form of 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene hemihydrate.
  • The complaint reserves the right to assert other claims.

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

  • Patent Identification: U.S. Patent No. 8,513,202, issued August 20, 2013.

The Invention Explained

  • Problem Addressed: As a continuation of the ’582 Patent, the ’202 Patent addresses the same technical challenge: the need for a pure, stable, and commercially reproducible crystalline form of canagliflozin for use in pharmaceutical products (ʼ202 Patent, col. 1:57-61).
  • The Patented Solution: The invention is the same crystalline hemihydrate form of canagliflozin disclosed in the parent patent, but it is claimed and characterized differently. The ’202 Patent uses analytical data, specifically from an infra-red (IR) spectrum, to define and identify the specific crystalline structure (’202 Patent, Abstract; col. 2:20-24).
  • Technical Importance: Defining a crystalline form by its unique spectral fingerprint (like an IR spectrum or X-ray diffraction pattern) provides an objective and quantitative method for identifying the polymorph and distinguishing it from other potential forms (’202 Patent, col. 1:50-56).

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claims 3-5 (Compl. ¶82).
  • Independent Claim 1:
    • 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.
  • The complaint reserves the right to assert other claims.

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are the generic drug products described in three separate Abbreviated New Drug Applications: Aurobindo ANDA No. 210386, InvaGen ANDA No. 210350, and Macleods ANDA No. 210380 (Compl. ¶1).

Functionality and Market Context

  • The ANDAs seek FDA approval to market generic versions of Plaintiffs’ INVOKANA® (canagliflozin) and INVOKAMET® (canagliflozin and metformin) drug products (Compl. ¶¶60, 65, 71). These drugs are used to improve glycemic control in adults with type 2 diabetes mellitus (Compl. ¶¶17-18). The act of infringement alleged in the complaint is the statutory act of filing the ANDAs for the purpose of obtaining approval to manufacture and sell these generic drugs before the expiration of the patents-in-suit (Compl. ¶76). The complaint alleges, on information and belief, that testing of the products described in the ANDAs will show that they contain the patented crystalline form of canagliflozin (Compl. ¶61).

IV. Analysis of Infringement Allegations

The complaint alleges that the Defendants' act of filing their respective ANDAs constitutes infringement under 35 U.S.C. § 271(e)(2). The underlying technical basis for this allegation is that the canagliflozin API in the proposed generic products is, or will be, the specific crystalline hemihydrate form claimed in the patents-in-suit.

'582 Patent 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 that the canagliflozin API contained in the proposed generic products described in Defendants' ANDAs is the claimed crystalline hemihydrate. ¶77, ¶87, ¶97 col. 1:7-13

'202 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A crystalline form of...hemihydrate having an infra-red spectrum in mineral oil comprising the following main peaks: 1626, 1600, 1549, and 1507 cm⁻¹. The complaint alleges that the canagliflozin API in the proposed generic products will, upon testing, exhibit an infra-red spectrum with the characteristic peaks required by the claim. ¶82, ¶92, ¶102 col. 3:20-24
  • Identified Points of Contention:
    • Technical Question: The central factual dispute will be whether the canagliflozin in the Defendants' proposed products is, in fact, the claimed crystalline hemihydrate. This will likely be resolved through scientific evidence, such as comparing the X-ray powder diffraction (XRPD) and IR spectra of the generic products against the data disclosed in the patents. The patents provide an exemplary XRPD pattern showing characteristic peaks that can be used for identification (’582 Patent, FIG. 1). The complaint notes that Defendants' notification letters allege non-infringement, suggesting that Defendants may contend their product contains a different, non-infringing polymorph of canagliflozin (Compl. ¶¶61, 66, 73).
    • Scope Questions: A likely point of dispute will be the scope of the claims. For example, claim 2 of the ’582 Patent defines the crystalline form by specific XRPD peaks with a margin of ±0.2 degrees 2θ (’582 Patent, col. 8:31-36). The litigation may turn on whether the analytical data from the accused products falls within these specified ranges or meets the definition of "substantially the same" pattern or spectrum, a term used in other claims (e.g., ’202 Patent, col. 2:31-35).

V. Key Claim Terms for Construction

  • The Term: "crystalline form of...hemihydrate"
  • Context and Importance: In a case concerning pharmaceutical polymorphs, the definition of the specific "crystalline form" is paramount. The entire infringement analysis depends on whether the accused generic products contain a crystal structure that meets this definition. Practitioners may focus on this term because the patents define it using multiple analytical characteristics (e.g., XRPD peaks, IR spectra), and any variance between the accused product and these defined characteristics could form the basis of a non-infringement defense.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: Plaintiffs may point to specification language stating that diffraction peak intensities can vary due to preferred orientation of crystals in a sample, arguing that "substantially the same" pattern should not require an exact match to the figures (’582 Patent, col. 2:55-59). This could support a finding of infringement even with minor differences in analytical data.
    • Evidence for a Narrower Interpretation: Defendants may argue that claims reciting specific numerical values, such as the 2θ values in claim 2 of the ’582 Patent or the IR peaks in claim 1 of the ’202 Patent, must be strictly met. They could argue that a generic product whose crystal form yields peaks outside the claimed ranges, even if close, does not literally infringe (’582 Patent, col. 8:31-36; ’202 Patent, col. 8:16-18).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Defendants' future commercial activities will induce and contribute to infringement by others (Compl. ¶¶77, 82). This is based on the premise that, if approved, Defendants will encourage and supply the infringing generic products to distributors, pharmacies, and ultimately patients for the patented uses.
  • Willful Infringement: While the complaint does not use the term "willful," it pleads that each Defendant had knowledge of the patents-in-suit at least as of the date they submitted their ANDAs or, for U.S. subsidiaries, no later than the date of service of the complaint (Compl. ¶¶78, 83, 88, 93, 98, 103). These allegations of knowledge are a required predicate for any future claim of willful infringement and potential enhanced damages.

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

This case presents a classic pharmaceutical patent dispute centered on a specific crystalline form of an active ingredient. The outcome will likely depend on the answers to two central questions:

  1. A core issue will be one of evidentiary proof: Can Plaintiffs demonstrate, through analytical techniques like X-ray diffraction and infrared spectroscopy, that the canagliflozin crystal form in Defendants' proposed generic products is the same "crystalline...hemihydrate" protected by the asserted claims?
  2. A second key question will be one of claim scope and validity: Assuming Defendants' products are not identical, how much variation does the claim language, such as "substantially the same" pattern, permit? Concurrently, the court will likely address Defendants' counter-allegations that the patents are invalid, potentially on grounds that the claimed crystalline form was obvious to discover or not adequately described in the patent.