Mitsubishi Tanabe Pharma Corp v. Teva Pharma USA Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Mitsubishi Tanabe Pharma Corporation (Japan), Janssen Pharmaceuticals, Inc. (Pennsylvania), Janssen Pharmaceutica NV (Belgium), Janssen Research and Development, LLC (New Jersey), and Cilag GmbH International (Switzerland)
  • Defendant: Teva Pharmaceuticals USA, Inc. (Delaware)
  • Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP; Quinn Emanuel Urquhart & Sullivan, LLP
• Case Identification: 1:17-cv-00998, D. Del., 07/21/2017
• Venue Allegations: Venue is alleged to be proper in the District of Delaware because the defendant, Teva, is a corporation organized and existing under the laws of Delaware.
• Core Dispute: Plaintiffs allege that Defendant’s 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 patents relate to a specific polymorphic form of canagliflozin, an SGLT2 inhibitor used to treat type 2 diabetes by causing excess glucose to be excreted in the urine.
• Key Procedural History: This action was initiated under the Hatch-Waxman Act following Plaintiffs' receipt of a letter from Teva, dated June 7, 2017, providing notice of Teva's ANDA filing. The patents-in-suit are listed in the FDA's "Orange Book" with respect to the INVOKANA® drug product. U.S. Patent No. 8,513,202 is a continuation of the application that resulted in U.S. Patent No. 7,943,582.

Case Timeline

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’s background section notes that for a chemical compound to be used commercially in a pharmaceutical product, it is important for it to have good handling qualities and be producible in a pure, stable, and crystalline form to meet exacting specifications; however, the patent notes that "there have been difficulties in obtaining a crystal form of the compound of formula (I) from organic solvents" (’582 Patent, col. 1:40-52).
• The Patented Solution: The invention is a specific crystalline hemihydrate form of the canagliflozin compound. The inventors discovered that this specific form "can be produced in a crystalline form in a manner reproducible on a commercial scale" and possesses "good handling qualities and characteristics" (’582 Patent, col. 1:53-58; col. 2:6-9). This specific crystal structure is characterized by data such as its X-ray powder diffraction pattern, shown in Figure 1 of the patent (’582 Patent, col. 2:64-65, FIG. 1).
• Technical Importance: The development of a stable and reproducible crystalline polymorph is a critical step in pharmaceutical development, as it ensures consistent purity, solubility, and bioavailability of the active ingredient in the final drug product (’582 Patent, col. 1:40-45).

Key Claims at a Glance

• The complaint asserts independent claim 1 and dependent claims 6 and 7 (Compl. ¶27).
• Independent 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-glucopyransoyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene hemihydrate," Issued August 20, 2013

The Invention Explained

• Problem Addressed: Similar to its parent patent, the ’202 Patent addresses the need for a stable, pure, and reproducible crystalline form of the canagliflozin compound suitable for commercial pharmaceutical manufacturing (’202 Patent, col. 2:1-12).
• The Patented Solution: The invention is the same crystalline hemihydrate form of canagliflozin, but the patent claims define it more specifically by its analytical characteristics. The solution is the specific crystalline form which, as described in the specification and claimed, can be identified by its characteristic infra-red (IR) spectrum, which serves as a fingerprint for the crystal structure (’202 Patent, col. 2:35-39; FIG. 2).
• Technical Importance: By defining the crystalline form with a specific analytical signature (the IR spectrum), the patent aims to precisely distinguish this commercially useful polymorph from other potential amorphous or crystalline forms of the same molecule (’202 Patent, col. 2:56-65).

Key Claims at a Glance

• The complaint asserts independent claim 1 and dependent claims 3-5 (Compl. ¶32).
• 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.

III. The Accused Instrumentality

• Product Identification: The accused instrumentality is the generic drug product described in Teva’s Abbreviated New Drug Application (ANDA) No. 210451 ("the Teva ANDA Product") (Compl. ¶1).
• Functionality and Market Context: The Teva ANDA Product is intended to be a generic version of Plaintiffs' INVOKANA® drug product, which is sold in 100 mg and 300 mg tablets (Compl. ¶1, ¶22). INVOKANA® contains the active pharmaceutical ingredient canagliflozin and is prescribed as an "adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus" (Compl. ¶14). The complaint alleges that the claims of the patents-in-suit "cover, inter alia, certain polymorphic forms of canagliflozin" and that Teva's proposed generic product will infringe these claims (Compl. ¶16, ¶23).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

The complaint alleges infringement based on Teva's ANDA submission under 35 U.S.C. § 271(e)(2) but does not provide a detailed claim chart or specific technical evidence. The infringement theory is that the product Teva seeks to market will contain the patented crystalline form of canagliflozin (Compl. ¶23, ¶27, ¶32).

’582 Patent Infringement Allegations

’202 Patent Infringement Allegations

• Identified Points of Contention:
  • Technical Question: The central dispute will be a factual one of polymorphic identification. Does the active pharmaceutical ingredient in the product specified by Teva’s ANDA actually possess the crystal structure of a "hemihydrate" as required by the claims? Evidence will likely involve competing analytical tests such as X-Ray Powder Diffraction (XRPD), Infra-Red (IR) spectroscopy, and thermogravimetric analysis (TGA).
  • Scope Question: For the ’202 Patent, a key question will be whether Teva's product exhibits an IR spectrum that meets the "comprising the following main peaks" limitation. For the ’582 Patent, which does not recite specific analytical data in its independent claim, a question arises as to how the "crystalline form" is defined and bounded, and how much deviation, if any, from the exemplary data in the specification is permitted for a finding of infringement.

V. Key Claim Terms for Construction

• The Term: "crystalline form ... hemihydrate"
• Context and Importance: This term is the central limitation of the asserted independent claims of both patents. The entire dispute hinges on whether Teva's proposed generic product is this specific polymorph, as distinguished from an amorphous form or other potential crystalline forms of canagliflozin. The "hemihydrate" component further limits the claim to a crystal lattice incorporating a specific ratio of water molecules. Practitioners may focus on this term because polymorphic identity is the dispositive issue in many pharmaceutical patent cases.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The patent specifications describe the invention in terms of its functional advantages, such as having "good handling qualities" and being "reproducible on a commercial scale" (’582 Patent, col. 1:40-58). A party could argue that the claims should be understood in light of these stated objectives, rather than being confined to an exact replication of the patent's examples.
  • Evidence for a Narrower Interpretation: Both patents provide highly specific analytical data to "characterize" the invention. The ’582 Patent presents a specific XRPD pattern (FIG. 1) and claims specific 2θ peak values in dependent claim 2 (’582 Patent, col. 8:31-38). The ’202 Patent explicitly includes IR peak values in its independent claim 1. A party could argue this data provides a precise and limiting "fingerprint" that an accused product must match to infringe.

VI. Other Allegations

• Indirect Infringement: The complaint alleges that if Teva commercially sells the ANDA product, it will induce and/or contribute to infringement by others, such as doctors and patients (Compl. ¶27, ¶32). This allegation is based on the premise that Teva's product label will instruct users to take the drug for its approved medical indication, thereby instructing them to perform an infringing use of the patented composition.
• Willful Infringement: While the complaint does not use the word "willful," it explicitly alleges that "Teva has had knowledge of the ’582 patent since at least the date it submitted the Teva ANDA" and makes an identical allegation regarding the ’202 Patent (Compl. ¶28, ¶33). These allegations of pre-suit knowledge of the patents-in-suit could form the basis for a later claim of willful infringement and a request for enhanced damages.

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

• A central issue will be one of polymorphic identity: Will discovery and testing demonstrate that the canagliflozin active ingredient specified in Teva's ANDA is, in fact, the specific "crystalline form...hemihydrate" claimed by the patents? This is a purely factual question that will be decided based on competing analytical evidence and expert testimony.
• A key legal and evidentiary question will be one of claim scope: For the ’202 patent, does the accused product's IR spectrum contain the four specific peaks recited in the claim? For the broader claim of the ’582 patent, the case may turn on how the court defines the boundaries of the claimed "crystalline form" and whether minor variations from the patent's exemplary characterization data are sufficient to avoid infringement.