DCT

1:18-cv-01689

Boehringer Ingelheim Pharma Inc v. Lupin Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:18-cv-01689, D. Del., 10/26/2018
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Lifestar Pharma LLC is a Delaware corporation and therefore "resides" in the district. Defendant Mankind Pharma Ltd. is a foreign corporation that may be sued 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 patent infringement.
  • Technical Context: The dispute involves pharmaceutical compositions and methods for treating type 2 diabetes, specifically concerning SGLT-2 inhibitors, a class of drugs that lower blood sugar by causing the kidneys to remove sugar from the body through urine.
  • Key Procedural History: The litigation was triggered by Defendants' submission of ANDA No. 212283 to the U.S. Food and Drug Administration. As part of that submission, Defendants provided a "Paragraph IV Certification" asserting that the patents-in-suit are either invalid or will not be infringed by the proposed generic products, creating the legal controversy for this Hatch-Waxman lawsuit.

Case Timeline

Date Event
2007-08-16 U.S. Patent No. 8,551,957 Priority Date
2013-04-05 U.S. Patent No. 9,949,998 Priority Date
2013-10-08 U.S. Patent No. 8,551,957 Issues
2018-04-24 U.S. Patent No. 9,949,998 Issues
2018-09-19 Plaintiffs receive Defendants' Paragraph IV Certification letter
2018-10-26 Complaint Filed

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

U.S. Patent No. 8,551,957 - “Pharmaceutical Composition Comprising a Glucopyranosyl-Substituted Benzene Derivate”

The Invention Explained

  • Problem Addressed: The patent addresses the need for new therapeutic options for type 2 diabetes mellitus, noting that existing treatments have limitations and that a significant portion of patients fail to achieve adequate glycemic control (’957 Patent, col. 8:49-61).
  • The Patented Solution: The invention is a pharmaceutical composition that combines two different classes of anti-diabetic drugs: a glucopyranosyl-substituted benzene derivative (an SGLT-2 inhibitor, which promotes urinary glucose excretion) and a DPP IV inhibitor (which increases insulin secretion and suppresses glucagon secretion) (’957 Patent, Abstract; col. 8:36-48). By combining these distinct mechanisms of action, the patented solution aims to achieve superior glycemic control compared to monotherapy with either agent alone (’957 Patent, col. 23:48-col. 24:11).
  • Technical Importance: The patent proposes a combination therapy that could offer a more comprehensive approach to managing the complex pathophysiology of type 2 diabetes, potentially improving outcomes for patients who do not respond adequately to single-agent treatments (’957 Patent, col. 8:49-61).

Key Claims at a Glance

  • The complaint asserts infringement of at least one claim without specifying which ones (Compl. ¶30). The first independent claim, Claim 1, is representative of the core invention.
  • The essential elements of asserted Claim 1 are:
    • A pharmaceutical composition comprising a specific glucopyranosyl-substituted benzene derivative: 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-((S)-tetrahydrofuran-3-yloxy)-benzyl]-benzene (a species of empagliflozin).
    • In combination with a specific DPP IV inhibitor: 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine (linagliptin), or a pharmaceutically acceptable salt thereof.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 9,949,998 - “Pharmaceutical Composition, Methods for Treating and Uses Thereof”

The Invention Explained

  • Problem Addressed: The patent identifies a challenge in treating type 2 diabetes in patients who also suffer from renal impairment or chronic kidney disease (CKD), as the use of many anti-diabetic agents is restricted or requires dose adjustments in this specific patient population (’998 Patent, col. 1:24-46).
  • The Patented Solution: The invention provides a method for treating type 2 diabetes in patients with a specific degree of kidney function, defined by an estimated glomerular filtration rate (eGFR). The method involves administering a specific oral dose of the SGLT-2 inhibitor empagliflozin to patients within a defined range of moderate renal impairment (’998 Patent, col. 2:47-52, Claim 1).
  • Technical Importance: This patented method provides a therapeutic protocol for a vulnerable sub-population of diabetic patients (those with moderate CKD), for whom treatment options may be limited due to safety or efficacy concerns with other medications (’998 Patent, col. 1:35-46).

Key Claims at a Glance

  • The complaint asserts infringement of at least one claim without specifying which ones (Compl. ¶41). The first independent claim, Claim 1, is representative.
  • The essential elements of asserted Claim 1 are:
    • A method for improving glycemic control in a patient with type 2 diabetes.
    • Administering empagliflozin to the patient if their eGFR is within the range of ≥45 ml/min/1.73 m² and <60 ml/min/1.73 m².
    • The empagliflozin is administered orally once daily in a 10 mg or 25 mg dose.
    • Wherein glycemic control is improved.
    • Discontinuing empagliflozin if the patient's eGFR falls below 45 ml/min/1.73 m².
  • The complaint does not explicitly reserve the right to assert dependent claims.

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are Defendants' proposed 10 mg and 25 mg empagliflozin tablets, for which ANDA No. 212283 was submitted to the FDA (the "Mankind ANDA Products") (Compl. ¶10).

Functionality and Market Context

The Mankind ANDA Products are a generic version of Plaintiffs' brand-name drug, JARDIANCE® (Compl. ¶1). The complaint alleges that Defendants' ANDA relies upon the JARDIANCE® New Drug Application and contains data intended to demonstrate bioequivalence between the proposed generic products and JARDIANCE® (Compl. ¶28). The act of filing the ANDA to seek approval for manufacturing and selling this generic version prior to the expiration of the patents-in-suit is the statutory act of infringement alleged under 35 U.S.C. § 271(e)(2) (Compl. ¶¶1, 11). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not contain a claim chart or provide sufficient detail for a formal claim chart analysis. The infringement allegations are based on the statutory act of infringement under 35 U.S.C. § 271(e)(2), which states that the submission of an ANDA constitutes infringement if the purpose of the submission is to obtain approval to market a drug claimed in a patent before its expiration (Compl. ¶11).

Infringement Theory for the ’957 Patent

The complaint alleges that the '957 patent "cover[s] the JARDIANCE® product and its use" (Compl. ¶25). Since JARDIANCE® contains only empagliflozin and the representative independent claim of the '957 Patent recites a composition with two active ingredients (empagliflozin and linagliptin), the infringement theory may rely on claims not analyzed in this report or, more likely, on a theory of indirect infringement. The complaint alleges that the Mankind ANDA Products, when used as directed by their label, would be used in a manner that directly infringes, and that Defendants' promotional materials and package inserts would actively induce infringement of at least one claim of the patent (Compl. ¶¶33, 37). This suggests a theory that Defendants will induce physicians to prescribe, and patients to use, generic empagliflozin in combination with a DPP IV inhibitor.

Infringement Theory for the ’998 Patent

The complaint alleges that the Mankind ANDA Products, when used as directed, would be used in a manner that directly infringes the method claims of the '998 Patent (Compl. ¶44). The infringement theory is one of induced infringement, wherein the product label for the generic empagliflozin will instruct physicians and patients to use the drug in a manner that practices the claimed method—specifically, for treating type 2 diabetes in patients within the eGFR ranges specified in the claims (Compl. ¶47). The submission of the ANDA with a proposed label that encourages this infringing use is the basis of the infringement claim (Compl. ¶41).

Identified Points of Contention

  • Scope Questions: For the ’957 Patent, a central question may be whether the asserted claims cover a product containing only empagliflozin, or if they are limited to the two-drug combination. If the latter, the case would turn on whether Defendants' actions constitute inducement to combine the generic product with a separate DPP IV inhibitor.
  • Technical Questions: For the ’998 Patent, a key question will be whether the proposed label for the Mankind ANDA Products will instruct or encourage use in the specific patient population defined by the eGFR range in the asserted claims. The content of the proposed label, which is not included in the complaint, will be critical evidence.

V. Key Claim Terms for Construction

The Term: "in combination with" (’957 Patent, Claim 1)

  • Context and Importance: This term is central because the accused product is a single-ingredient tablet (empagliflozin), while Claim 1 of the '957 Patent recites a composition of that ingredient "in combination with" a second, different ingredient (linagliptin). The construction of this term will determine whether the claim requires the two active ingredients to be co-formulated in a single composition or if it can cover, for example, a kit containing separate tablets or a regimen of concurrent administration.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification discusses administering the components "in combination or alternation" (’957 Patent, col. 9:16-18) and contemplates separate dosage forms, which could support a construction that does not require co-formulation (’957 Patent, col. 29:2-13).
    • Evidence for a Narrower Interpretation: The claim preamble recites a "pharmaceutical composition," which typically implies a single formulation. The language "comprising... [drug A] in combination with [drug B]" within the body of a composition claim may be argued to require the physical presence of both ingredients in the claimed composition.

The Term: "improving glycemic control" (’998 Patent, Claim 1)

  • Context and Importance: This is a method claim limitation that defines the outcome of the administration step. Practitioners may focus on this term because its definition is critical to the infringement analysis, particularly for inducement. The dispute may center on what level of "improvement" is required and how it must be demonstrated or instructed on the proposed generic label.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification describes "improving glycemic control" in general terms, such as reducing fasting plasma glucose, postprandial plasma glucose, and/or glycosylated hemoglobin HbA1c (’998 Patent, col. 2:1-4). This may support a broad interpretation covering any statistically significant improvement.
    • Evidence for a Narrower Interpretation: The patent includes clinical trial data showing specific levels of HbA1c reduction in patients with renal impairment (’998 Patent, FIG. 1A, FIG. 7A). A defendant might argue that "improving glycemic control" should be construed in light of these disclosed results, requiring a specific quantum of improvement to meet the claim limitation.

VI. Other Allegations

Indirect Infringement

The complaint alleges both induced and contributory infringement for both patents. It asserts that Defendants know their product is especially adapted for infringing use and that their promotional materials and package inserts will instruct users to perform the infringing acts (Compl. ¶¶34, 37, 45, 47). These allegations are central to the case, particularly for the method-of-use claims in the '998 Patent and any combination-therapy claims in the '957 Patent.

Willful Infringement

The complaint does not contain an explicit allegation of willful infringement. However, it alleges that the case is "exceptional" under 35 U.S.C. § 285 and seeks an award of attorneys' fees, based on Defendants' filing of the ANDA with knowledge of the patents (Compl. ¶¶39, 51; Prayer for Relief ¶b).

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

  • A core issue will be one of indirect infringement for combination therapy: For the ’957 Patent, can Plaintiffs prove that Defendants' proposed marketing of a single-ingredient empagliflozin product will induce physicians to prescribe it as part of an infringing combination therapy with a separate DPP IV inhibitor, as claimed in the patent?
  • A second key issue will be one of label-based inducement for a method of use: For the ’998 Patent, does the proposed product label for Defendants’ generic empagliflozin contain instructions or information that would inevitably lead a substantial number of physicians to prescribe it for patients within the specific renal impairment (eGFR) ranges recited in the claims?
  • Finally, a foundational question underlying the entire dispute, raised by Defendants' Paragraph IV certification, will be the validity of the asserted patent claims: Will Defendants be able to prove by clear and convincing evidence that the asserted claims of the ’957 and ’998 patents are invalid on grounds such as obviousness or lack of written description?