DCT
1:18-cv-00292
Mitsubishi Tanabe Pharma Corp v. Lupin Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Mitsubishi Tanabe Pharma Corporation (Japan)
- Defendant: Lupin Limited (India)
- Plaintiff’s Counsel: Saul Ewing Arnstein & Lehr LLP
- Case Identification: 1:18-cv-00292, D.N.J., 01/09/2018
- Venue Allegations: Plaintiffs allege venue is proper because Defendant Lupin India is a foreign corporation subject to personal jurisdiction in the district, and Defendant Lupin Pharmaceuticals maintains a regular and established place of business in the district. Jurisdiction is based on Defendants’ business activities in New Jersey and, specifically, the act of filing Abbreviated New Drug Applications (ANDAs) seeking to market generic products in the U.S., including New Jersey.
- Core Dispute: Plaintiffs allege that Defendants’ submission of ANDAs to the FDA for approval to market generic versions of the diabetes drugs Invokana® and Invokamet® constitutes an act of infringement of two patents covering a specific crystalline hemihydrate form of the active ingredient, canagliflozin.
- Technical Context: The technology concerns a specific polymorphic form (a crystalline hemihydrate) of canagliflozin, an SGLT2 inhibitor used to treat type 2 diabetes, which is asserted to provide enhanced stability and manufacturing reproducibility over other forms.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Plaintiffs' receipt of notice letters concerning Defendants' ANDA filings. The complaint notes that other lawsuits involving the same patents have been filed against different generic pharmaceutical manufacturers, indicating ongoing, multi-front litigation to defend the patented technology.
Case Timeline
| Date | Event |
|---|---|
| 2006-12-04 | Priority Date for ’582 and ’202 Patents |
| 2011-05-17 | U.S. Patent No. 7,943,582 Issues |
| 2013-08-20 | U.S. Patent No. 8,513,202 Issues |
| 2017-11-27 | Date of Lupin's Notice Letter for ANDA No. 211103 |
| 2017-12-14 | Date of Lupin's Notice Letter for ANDA No. 211104 |
| 2018-01-09 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,943,582
- 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.
The Invention Explained
- Problem Addressed: The patent's background section notes that while the active pharmaceutical ingredient (API), canagliflozin, was known, there were "difficulties in obtaining a crystal form of the compound...from organic solvents" (’582 Patent, col. 2:47-49). For commercial pharmaceutical products, it is important to have a pure, stable, and reproducible form of the API to ensure consistent quality and facilitate formulation (’582 Patent, col. 2:40-46).
- The Patented Solution: The patent discloses a novel crystalline "hemihydrate" of the canagliflozin compound (’582 Patent, col. 2:54-58). This specific crystalline structure, which incorporates water molecules, is described as having "good handling qualities and characteristics" and being producible "in a manner reproducible on a commercial scale" (’582 Patent, col. 2:9-12). The structure is primarily defined by its unique X-ray powder diffraction (XRPD) pattern, as illustrated in Figure 1 of the patent.
- Technical Importance: The creation of a stable and reproducible crystalline form of an API is a critical step in drug development, enabling consistent manufacturing, predictable dissolution rates, and improved shelf life for the final pharmaceutical product (’582 Patent, col. 2:40-46).
Key Claims at a Glance
- The complaint asserts independent claim 1 and dependent claims 6 and 7 (Compl. ¶¶49, 50).
- Independent Claim 1:
- A crystalline form of 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene hemihydrate.
- The complaint alleges infringement of "at least" these claims, reserving the right to assert others.
U.S. Patent No. 8,513,202
- Patent Identification: 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, this patent addresses the same technical problem: the need for a stable, pure, and commercially viable crystalline form of canagliflozin where previous efforts had faced difficulties (’202 Patent, col. 2:50-59).
- The Patented Solution: The invention is the same crystalline hemihydrate form of canagliflozin disclosed in the ’582 patent. However, this patent's claims define the crystalline form using a different analytical technique: its infra-red (IR) spectrum (’202 Patent, col. 3:20-24). Figure 2 of the patent shows the characteristic IR spectrum that identifies the claimed crystalline form.
- Technical Importance: As with the ’582 patent, this invention provides a specific, stable polymorph of the canagliflozin API, which is essential for developing a reliable and effective pharmaceutical product for market (’202 Patent, col. 2:50-55).
Key Claims at a Glance
- The complaint asserts independent claim 1 and dependent claims 3-5 (Compl. ¶¶56, 57).
- 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 alleges infringement of "at least" these claims, reserving the right to assert others.
III. The Accused Instrumentality
Product Identification
- The accused instrumentalities are the proposed generic drug products described in Lupin's ANDA No. 211103 (a generic version of Invokana®) and ANDA No. 211104 (a generic version of Invokamet®) (Compl. ¶1).
Functionality and Market Context
- The Lupin ANDA Products are intended to be generic equivalents of Plaintiffs' branded drugs, which contain canagliflozin (and metformin, in the case of Invokamet®) and are prescribed to improve glycemic control in adults with type 2 diabetes mellitus (Compl. ¶¶15-16, 36, 42). The complaint alleges, on information and belief, that the canagliflozin API in Lupin's proposed products is the specific crystalline hemihydrate form covered by the patents-in-suit (Compl. ¶¶49-50, 56-57). The complaint notes Lupin's position as a major generics pharmaceutical company, suggesting an intent to capture a significant share of the market for these diabetes treatments upon FDA approval (Compl. ¶22).
IV. Analysis of Infringement Allegations
The complaint does not provide detailed infringement contentions or a claim chart. The infringement allegations are based on the statutory act of filing the ANDAs and on Plaintiffs' stated "information and belief" that the products described therein will infringe.
’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 discovery and testing will show that the Lupin ANDA Products are, or contain, the claimed crystalline hemihydrate form of canagliflozin. The XRPD pattern shown in Figure 1 of the patent is a key characteristic of this form. | ¶49, ¶50 | col. 2:7-12 |
’202 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 having an infra-red spectrum in mineral oil comprising the following main peaks: 1626, 1600, 1549, and 1507 cm⁻¹. | The complaint alleges that discovery and testing will show that the canagliflozin in the Lupin ANDA Products has an IR spectrum with the claimed peaks, thereby infringing the claim. The IR spectrum shown in Figure 2 of the patent is a key characteristic of this form. | ¶56, ¶57 | col. 3:10-14 |
- Identified Points of Contention:
- Factual Question: The central dispute will be factual: Does the canagliflozin API in Lupin's ANDA products possess the specific crystalline structure of a hemihydrate as claimed in the patents? The case will likely depend on the results of analytical tests (e.g., XRPD, IR spectroscopy, thermogravimetric analysis) performed on samples of Lupin's proposed product.
- Scope Question: A key question for the court will be the degree of identity required between the analytical data for Lupin's product and the data presented in the patents. This raises the question of whether any observed differences in analytical signatures (e.g., XRPD peak positions/intensities or IR peak wavenumbers) are sufficient to place Lupin's product outside the scope of the claims.
V. Key Claim Terms for Construction
The Term: "crystalline form ... hemihydrate"
Context and Importance: This term is the foundation of the patents-in-suit, as the invention is not the canagliflozin molecule itself but this specific solid-state form. The dispute will turn on whether Lupin's product is, in fact, this particular form. Practitioners may focus on this term because the existence of different polymorphs or solvates is common for pharmaceutical compounds, and proving that an accused product contains the exact patented form is the crux of such litigation.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patents do not appear to offer language supporting a broad interpretation; the invention is defined by its specific, measured characteristics.
- Evidence for a Narrower Interpretation: The specifications of both patents tie the definition of the crystalline form to highly specific analytical data. The ’582 patent provides a dependent claim (Claim 2) defining the form by five specific XRPD 2θ values (’582 Patent, col. 8:35-41). The ’202 patent's independent claim 1 defines the form by four specific IR spectrum peaks (’202 Patent, col. 8:16-18). This data provides a precise, narrow fingerprint for the claimed material.
The Term: "having substantially the same [X-ray diffraction pattern / IR spectrum] as set out in [FIG. 1 / FIG. 2]" (from dependent claims in both patents, e.g., '582 Patent, Claim 3)
Context and Importance: The word "substantially" is a classic term of degree that is frequently litigated. Its construction will determine how much deviation from the patent's exemplary figures is allowed before an accused product is considered non-infringing.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: Plaintiffs may point to specification language stating that "diffraction peak intensities in the experimental patterns can vary...due to preferred orientation (non-random orientation of the crystals) in the prepared sample" (’582 Patent, col. 2:55-59). This suggests that the invention is not limited to an exact replica of the figure and that some variation is expected and covered.
- Evidence for a Narrower Interpretation: Defendants may argue that "substantially" requires a very close match, and that the term was only intended to cover minor, unavoidable experimental noise. They may contend that any structurally significant differences in peak positions or the appearance of new peaks would indicate a different, non-infringing polymorph.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Lupin will induce and contribute to infringement by commercially marketing its generic products (Compl. ¶¶49-50, 56-57). The alleged basis for inducement is the product labeling that will instruct physicians and patients to use the drug for its approved indication, which would constitute an infringing use of the patented crystalline form.
- Willful Infringement: The complaint does not use the term "willful." However, it does plead that Lupin had knowledge of the patents at least as of the date it submitted its ANDAs, and that Lupin Pharmaceuticals will have knowledge upon service of the complaint (Compl. ¶¶51, 58). These allegations of pre-suit and post-suit knowledge could form the basis for a later claim for enhanced damages should infringement be found.
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of factual identity: Will the physical and chemical characterization of Lupin's proposed generic API, through analytical techniques like XRPD and IR spectroscopy, prove that it is the same "crystalline...hemihydrate" form claimed in the patents-in-suit, or will it reveal a different, non-infringing polymorph?
- A key legal question will be one of definitional precision: In construing the claims, how much variance will the court permit under the term "substantially the same" when comparing Lupin's product data to the figures and peak values disclosed in the patents? The outcome of this claim construction will set the evidentiary bar for proving infringement.