DCT

1:21-cv-01487

Boehringer Ingelheim Pharma Inc v. Sun Pharmaceutical Industries Ltd

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:21-cv-01487, D. Del., 10/22/2021
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because each Defendant is incorporated in the state and therefore "resides" in the district.
  • Core Dispute: Plaintiff alleges that Defendant's submission of Abbreviated New Drug Applications (ANDAs) seeking to market generic versions of Plaintiff's empagliflozin-based diabetes drugs constitutes an act of infringement of a patent covering methods of using the drug in specific patient populations.
  • Technical Context: The technology relates to SGLT-2 inhibitors, a class of oral medications for type 2 diabetes, and specifically their use in patients who also suffer from chronic kidney disease, a common and complicating comorbidity.
  • Key Procedural History: This is a Hatch-Waxman action filed in response to a Paragraph IV certification notice letter, received by Plaintiff on or about September 30, 2021, in which Defendant asserted that the patent-in-suit is invalid or would not be infringed by its proposed generic products.

Case Timeline

Date Event
2013-04-05 U.S. Patent No. 11,090,323 Priority Date
2021-08-17 U.S. Patent No. 11,090,323 Issue Date
2021-09-30 Plaintiff receives Defendant's Paragraph IV Notice Letter
2021-10-22 Complaint Filing Date

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

U.S. Patent No. 11,090,323 - Pharmaceutical composition, methods for treating and uses thereof

  • Patent Identification: U.S. Patent No. 11,090,323 ("the '323 Patent"), titled Pharmaceutical composition, methods for treating and uses thereof, issued on August 17, 2021.

The Invention Explained

  • Problem Addressed: The patent's background section describes the challenge of treating type 2 diabetes mellitus (T2DM) in patients who also have renal impairment or chronic kidney disease (CKD). It notes that the use of many standard anti-diabetic agents is restricted in these patients due to safety concerns or reduced efficacy, creating a need for effective treatment options for this population ('323 Patent, col. 1:23-49).
  • The Patented Solution: The invention is a method of treating T2DM by administering empagliflozin, an SGLT-2 inhibitor, to patients with specific, defined levels of moderate renal impairment. The patent discloses clinical trial data to demonstrate that this method improves glycemic control (as measured by HbA1c, for example) in this specific patient subgroup, who might otherwise have limited treatment options ('323 Patent, Abstract; col. 2:50-65; Fig. 1A).
  • Technical Importance: The claimed method provides a therapeutic option for a significant and difficult-to-treat diabetic patient population where other common medications may be contraindicated or require dose adjustments ('323 Patent, col. 1:35-44).

Key Claims at a Glance

  • The complaint does not specify which claims it asserts, but independent claims 1 and 25 are representative of the core invention.
  • Independent Claim 1:
    • A method for improving glycemic control in a patient with type 2 diabetes mellitus
    • comprising administering empagliflozin to the patient if the patient's estimated glomerular filtration rate (eGFR) is ≥45 ml/min/1.73 m² and <60 ml/min/1.73 m² (i.e., moderate A renal impairment),
    • wherein empagliflozin is administered orally in a total daily amount of 10 mg or 25 mg,
    • wherein the glycemic control in the patient is improved, and
    • discontinuing empagliflozin if the patient's eGFR falls below 30 ml/min/1.73 m².
  • Independent Claim 25:
    • A method for improving glycemic control in a patient with type 2 diabetes mellitus
    • comprising administering empagliflozin to the patient if the patient's eGFR is ≥30 ml/min/1.73 m² and <60 ml/min/1.73 m² (i.e., moderate A and B renal impairment),
    • wherein empagliflozin is administered orally in a total daily amount of 10 mg or 25 mg,
    • wherein the glycemic control in the patient is improved, and
    • discontinuing empagliflozin if the patient's eGFR falls below 30 ml/min/1.73 m².
  • The complaint reserves the right to assert infringement of any of the patent's claims (Compl. ¶53).

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are Defendant's proposed generic drug products detailed in four ANDAs: No. 212343 (empagliflozin), No. 212339 (empagliflozin/linagliptin), No. 215529 (empagliflozin/metformin extended-release), and No. 214843 (empagliflozin/linagliptin/metformin extended-release) (Compl. ¶¶ 11-14).

Functionality and Market Context

The complaint alleges that Defendant's ANDA products are generic versions of Plaintiff's branded drugs JARDIANCE®, GLYXAMBI®, SYNJARDY® XR, and TRIJARDY® XR, respectively (Compl. ¶1). It is further alleged that Defendant has represented its products are bioequivalent to the corresponding branded drugs (Compl. ¶48, ¶63, ¶78, ¶93). The act of infringement alleged under the Hatch-Waxman Act is the submission of the ANDAs themselves, which seek FDA approval to market these generic products for uses that are covered by the '323 Patent before its expiration (Compl. ¶50). Figure 1A of the patent, attached as an exhibit to the complaint, presents clinical data demonstrating a statistically significant reduction in HbA1c (a measure of glycemic control) in patients with moderate renal impairment treated with empagliflozin (Compl., Ex. A, '323 Patent, Fig. 1A).

IV. Analysis of Infringement Allegations

The complaint does not contain a claim chart. The analysis below is based on the asserted claims and the infringement theory for induced infringement, which alleges that the label for the accused products will instruct users to perform the patented method.

’323 Patent Infringement Allegations (Representative Claim 1)

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 administering empagliflozin to the patient... Defendant's proposed generic empagliflozin products are intended for use in treating type 2 diabetes mellitus, and their labels are expected to instruct this use. ¶54 col. 39:50-52
...if the eGFR of the patient is ≥45 ml/min/1.73 m² and <60 ml/min/1.73 m²... Defendant's product label will allegedly instruct or otherwise encourage administration of the drug to patients within this specific sub-population with moderate renal impairment. ¶58 col. 39:52-54
...wherein empagliflozin is administered orally in a total daily amount of 10 mg or 25 mg... Defendant's ANDAs seek approval to market empagliflozin tablets in 10 mg and 25 mg dosages. ¶11 col. 39:55-57
...wherein the glycemic control in said patient is improved... As a bioequivalent product, Defendant's generic is expected to produce the same improvement in glycemic control as the branded drug, an effect demonstrated in the patent's clinical trial data. ¶48 col. 39:57-59
...and discontinuing empagliflozin if the eGFR of the patient falls below 30 ml/min/1.73 m². The product label is expected to include instructions to stop treatment if a patient's renal function declines below this threshold, in line with established clinical practice for the molecule. ¶58 col. 39:59-62

Identified Points of Contention

  • Scope Questions (Induced Infringement): A primary issue for induced infringement will be the specific language of Defendant's proposed product label. The court will need to determine if the label's instructions and indications for use would lead a physician to prescribe the drug in a manner that satisfies all limitations of the asserted method claims, particularly the specific eGFR ranges. Plaintiff alleges that Defendant intends to engage in promotional activities that would aid and abet infringement (Compl. ¶57).
  • Technical Questions (Direct Infringement): The underlying question of direct infringement will turn on whether administering the drug to a patient in the claimed eGFR range results in "improved glycemic control." The patent itself provides significant evidence in the form of clinical trial data. For example, Figure 7A of the patent shows a statistically significant, placebo-adjusted mean decrease in HbA1c of -0.54% at 52 weeks for patients in the CKD stage 3A group (eGFR ≥45 to <60), which directly supports this claim limitation (Compl., Ex. A, '323 Patent, Fig. 7A). Sun's alleged representation of bioequivalence will likely be used by Boehringer to argue that Sun's product would necessarily achieve the same result (Compl. ¶48).

V. Key Claim Terms for Construction

"improving glycemic control"

  • Context and Importance: This term defines the required outcome of the patented method. Its construction is critical because it sets the standard for what constitutes infringement. The dispute may focus on whether any statistically significant improvement suffices, or if a more substantial "clinically meaningful" threshold is required.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification lists several metrics for glycemic control, including reducing fasting plasma glucose, postprandial plasma glucose, and glycosylated hemoglobin HbA1c ('323 Patent, col. 2:2-5). The clinical data in the patent's figures shows various levels of statistically significant improvement, which may support an interpretation that any such demonstrated improvement meets the claim limitation (Compl., Ex. A, '323 Patent, Fig. 1A).
    • Evidence for a Narrower Interpretation: The detailed description of the clinical trials, which served as the basis for the invention, focuses on specific primary endpoints like "change from baseline in HbA1c at week 24" ('323 Patent, col. 46:60-62). A party could argue that "improving glycemic control" should be interpreted in light of these specific, measured outcomes, potentially requiring a certain quantum of improvement.

"eGFR of the patient"

  • Context and Importance: This phrase defines the specific patient population to which the method applies. Practitioners may focus on this term because the method of calculating eGFR could determine whether a particular patient falls inside or outside the claimed ranges.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification states that the "estimated glomerular filtration rate (eGFR)" is derived from serum creatinine values based on, "e.g., the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, the Cockcroft-Gault formula or the Modification of Diet in Renal Disease (MDRD) formula" ('323 Patent, col. 17:45-51). The use of "e.g." suggests this list is not exhaustive and could encompass any medically accepted formula for estimating GFR.
    • Evidence for a Narrower Interpretation: The patent's own examples detailing the clinical trials repeatedly specify that the MDRD formula was used to calculate the eGFR for patient inclusion and analysis ('323 Patent, col. 46:51-53; col. 47:18-21). A party could argue that the claims should be limited to the specific methodology disclosed and exemplified in the patent.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement. Inducement is based on the allegation that Defendant's promotional activities and package inserts will instruct physicians and patients to use the generic products in a manner that directly infringes the '323 Patent (Compl. ¶57-58, ¶72-73). Contributory infringement is based on the allegation that the products are "especially made or adapted for use in infringing" and are not staple articles of commerce with substantial non-infringing uses (Compl. ¶55-56, ¶70-71).
  • Willful Infringement: The complaint makes conclusory allegations of willfulness, stating that Defendant had knowledge of the '323 Patent, and seeks enhanced damages (Compl. ¶57). In the context of ANDA litigation, this knowledge is typically established by the patent's listing in the FDA's Orange Book and the Defendant's own Paragraph IV certification notice.

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

  • A central issue will be one of induced infringement: Will the specific language in Sun's proposed generic drug label be found to actively instruct or encourage physicians to prescribe empagliflozin for the patient population defined by the precise eGFR boundaries of the asserted claims?
  • The case will likely turn on claim construction and validity: Can Boehringer defend the non-obviousness of its claims, which are defined by specific numerical eGFR ranges, against prior art that may have disclosed the general use of SGLT-2 inhibitors in patients with some degree of renal impairment? The outcome may depend on whether these specific ranges are viewed as an inventive selection yielding unexpected results or an obvious optimization.
  • A key evidentiary question will be one of infringement and bioequivalence: While the '323 patent provides its own clinical data showing "improved glycemic control" (e.g., Fig. 7A), will Sun's admission of bioequivalence be sufficient to meet Plaintiff's burden of proving that the accused products, when used as directed, would necessarily perform the patented method and achieve the claimed result?