DCT

1:19-cv-01498

Boehringer Ingelheim Pharma Inc v. Mankind Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:19-cv-01498, D. Del., 08/09/2019
  • Venue Allegations: Venue is asserted in the District of Delaware based on Defendant Lifestar Pharma LLC being a Delaware corporation, and Defendant Mankind Pharma Ltd. being a foreign corporation subject to suit in any judicial district.
  • Core Dispute: Plaintiff alleges that Defendants’ filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's JARDIANCE® (empagliflozin) tablets constitutes an act of infringement of a patent directed to methods of using the drug in specific patient populations.
  • Technical Context: The technology at issue involves methods for treating type 2 diabetes mellitus in patients who also have moderate renal (kidney) impairment, a patient group for whom many standard diabetes treatments are restricted.
  • Key Procedural History: The complaint states that the litigation was precipitated by a Paragraph IV certification letter, received by Plaintiff on or about May 3, 2019, in which Defendants asserted that the patent-in-suit is invalid or would not be infringed by their proposed generic product.

Case Timeline

Date Event
2013-04-05 U.S. Patent No. 10,258,637 Priority Date
2019-04-16 U.S. Patent No. 10,258,637 Issues
2019-05-03 Plaintiff receives Defendant's Paragraph IV Letter
2019-08-09 Complaint Filed

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

  • Patent Identification: U.S. Patent No. 10,258,637, "Pharmaceutical Composition, Methods for Treating and Uses Thereof," issued April 16, 2019. (Compl. ¶20; '637 Patent, cover page).
  • The Invention Explained:
    • Problem Addressed: The patent's background section describes the challenge of treating type 2 diabetes in patients with co-existing renal impairment or chronic kidney disease (CKD). It notes that the use of many anti-diabetes agents is restricted or requires dose adjustments in this patient population, creating a need for effective treatment options. ('637 Patent, col. 1:29-48).
    • The Patented Solution: The invention provides methods of using the SGLT-2 inhibitor empagliflozin to improve glycemic control in type 2 diabetes patients who have specific, defined levels of moderate renal impairment. The claimed methods involve administering empagliflozin to patients whose estimated glomerular filtration rate (eGFR) falls within a specified range, and discontinuing the drug if the patient's renal function declines below a certain threshold. ('637 Patent, Abstract; col. 2:37-48).
    • Technical Importance: The patented methods aim to provide a safe and effective therapeutic pathway for a specific patient sub-population for whom treatment options are otherwise limited due to renal dysfunction. ('637 Patent, col. 1:36-48).
  • Key Claims at a Glance:
    • The complaint asserts infringement of at least one claim of the '637 patent. Independent claim 1 is representative of the asserted method claims. (Compl. ¶29).
    • The essential elements of independent claim 1 are:
      • A method for improving glycemic control in a patient with type 2 diabetes mellitus.
      • Administering empagliflozin to the patient if their eGFR is ≥45 ml/min/1.73 m² and <60 ml/min/1.73 m².
      • Administering empagliflozin orally in a total daily amount of 5 mg, 10 mg, 12.5 mg, or 25 mg.
      • Achieving improved glycemic control in the patient.
      • Discontinuing empagliflozin if the patient's eGFR falls below 45 ml/min/1.73 m².
    • The complaint does not specify assertion of dependent claims but makes a general allegation of infringement of "at least one claim." (Compl. ¶29).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentalities are Defendants' 10 mg and 25 mg empagliflozin tablets, for which Defendants submitted Abbreviated New Drug Application (ANDA) No. 212283 to the FDA. (Compl. ¶10).
  • Functionality and Market Context:
    • The Mankind ANDA Products are generic versions of Plaintiff's JARDIANCE® tablets and contain the same active pharmaceutical ingredient, empagliflozin. (Compl. ¶1). The complaint alleges that Defendants' ANDA relies on the clinical data from Plaintiff's New Drug Application for JARDIANCE® and that Defendants' product is bioequivalent. (Compl. ¶27). The infringement allegation is based on the submission of the ANDA itself as an act of infringement under 35 U.S.C. § 271(e)(2), and the future commercial manufacture and sale of the product for the patented use. (Compl. ¶¶29, 31).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

  • Claim Chart Summary: The complaint does not include a claim chart. The infringement theory is that Defendants' proposed product label will instruct medical professionals and patients to use the generic empagliflozin tablets in a manner that performs all the steps of the patented method.

'637 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for improving glycemic control in a patient with type 2 diabetes mellitus comprising: The complaint alleges that the '637 patent "covers the use of JARDIANCE®" and that Defendants' proposed generic product, upon approval, would be used in a manner that directly infringes. The proposed product label is expected to indicate its use for treating type 2 diabetes. ¶¶24, 32 col. 37:37-39
administering empagliflozin to the patient if the eGFR of the patient is ≥45 ml/min/1.73 m² and <60 ml/min/1.73 m² It is alleged that the instructions for use accompanying the Mankind ANDA Products will direct or encourage administration to patients with moderate renal impairment falling within the claimed eGFR range. ¶¶32, 35 col. 37:40-42
wherein empagliflozin is administered orally in a total daily amount of 5 mg, 10 mg, 12.5 mg or 25 mg Defendants' ANDA seeks approval for 10 mg and 25 mg oral tablets, which correspond to dosages specified in the claim. ¶10 col. 37:42-44
wherein the glycemic control in said patient is improved The proposed product label is expected to promote the product as effective for improving glycemic control, which is the intended outcome of the claimed method. ¶¶24, 32 col. 37:45-46
and discontinuing empagliflozin if the eGFR of the patient falls below 45 ml/min/1.73 m² It is alleged that the instructions for use for the Mankind ANDA Products will direct or encourage discontinuation of the drug if a patient's renal function declines to the level specified in the claim. ¶¶32, 35 col. 37:46-48
  • Identified Points of Contention:
    • Scope Questions: A primary point of contention may be whether the language of the proposed label for the Mankind ANDA Products will instruct or encourage users to perform every step of the asserted method claim. The analysis will depend on the precise wording of the label regarding patient selection based on eGFR and the instructions related to discontinuing the drug.
    • Technical Questions: A key evidentiary question will be whether Defendants' proposed label creates liability for induced infringement. This raises the question of whether the label merely provides information about the drug's performance in certain patient populations or actively instructs physicians to follow the patented method, including the specific "administering" and "discontinuing" steps based on eGFR thresholds.

V. Key Claim Terms for Construction

  • The Term: "discontinuing empagliflozin"

  • Context and Importance: This term represents an affirmative action step required to practice the claimed method. Infringement of the method claim requires this step to be performed or, in the context of inducement, for the product label to instruct this step. The construction of "discontinuing" will be critical to determining whether a product label that contains warnings or recommendations, rather than an explicit command, meets this limitation.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: A plaintiff may argue that in the context of a package insert, language advising, recommending, or cautioning against use below a certain eGFR is legally sufficient to be an instruction that induces infringement of the "discontinuing" step, as physicians would interpret it as a direction to stop treatment.
    • Evidence for a Narrower Interpretation: The patent uses the active verb "discontinuing" in the claims without further definition. ('637 Patent, col. 37:46-47). A defendant could argue this requires its plain and ordinary meaning: a direct instruction to cease administration, and that weaker language on a label, such as a warning or a statement that efficacy may be reduced, does not meet this limitation.

  • The Term: "improving glycemic control"

  • Context and Importance: This phrase defines the intended result and utility of the claimed method. Practitioners may focus on this term because its definition could set the bar for what constitutes successful practice of the method, which could be relevant to infringement and validity.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification describes improvement in glycemic control by referencing reductions in multiple metrics, including fasting plasma glucose, postprandial plasma glucose, and glycosylated hemoglobin (HbA1c). ('637 Patent, col. 2:1-4). This could support a construction where a statistically significant improvement in any one of these metrics suffices.
    • Evidence for a Narrower Interpretation: The patent includes extensive clinical trial data in its figures (e.g., FIG. 1A, FIG. 7A) showing specific mean reductions in HbA1c. A defendant might argue that "improving" should be construed to require a level of improvement that is clinically meaningful, potentially tying the term's scope to the results disclosed in the patent's own examples.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement. The basis for inducement is the allegation that Defendants' promotional activities and package inserts for the ANDA products will instruct users to perform the patented method. (Compl. ¶35, 36). The basis for contributory infringement is the allegation that the ANDA products are especially adapted for infringing use and are not staple articles of commerce suitable for substantial non-infringing use. (Compl. ¶33).
  • Willful Infringement: The complaint alleges that Defendants had knowledge of the '637 patent, at the latest, upon sending the Paragraph IV certification letter. (Compl. ¶¶28, 35). Plaintiff seeks a finding that the case is "exceptional" under 35 U.S.C. § 285, which is the statutory basis for an award of attorney's fees and is often predicated on a finding of willful infringement. (Compl. ¶39).

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

  • A central issue will be one of label-based infringement: will the final, FDA-approved label for Defendants' generic empagliflozin product contain language that actively instructs or encourages physicians and patients to perform all steps of the patented method? The case may turn on whether the label's directions for use, particularly regarding patient selection by eGFR and discontinuation of therapy, are coextensive with the limitations of an asserted claim.
  • A key legal question will be one of claim construction and inducement: can the method step "discontinuing empagliflozin" be met by label language that warns against use or notes reduced efficacy in patients below a certain eGFR threshold, or does the claim require an explicit and mandatory instruction to stop the drug? The court's interpretation of this active step will likely be dispositive for the induced infringement analysis.