Boehringer Ingelheim Pharma Inc v. Ajanta Pharma Ltd

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Boehringer Ingelheim Pharmaceuticals Inc. (Delaware)
  • Defendant: Ajanta Pharma Limited (India)
  • Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
• Case Identification: 1:23-cv-00847, D. Del., 08/04/2023
• Venue Allegations: Venue is alleged to be proper on the basis that Defendant is a foreign corporation not residing in any U.S. judicial district and has previously litigated Hatch-Waxman patent disputes in the District of Delaware.
• Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application to the FDA for a generic version of Plaintiff’s GLYXAMBI® product constitutes an act of infringement of four patents related to pharmaceutical compositions and methods of treating diabetes.
• Technical Context: The technology concerns oral pharmaceutical compositions combining an SGLT2 inhibitor (empagliflozin) and a DPP-IV inhibitor (linagliptin) for the treatment of type 2 diabetes, including in specific patient populations such as those with renal impairment.
• Key Procedural History: The litigation was initiated under the Hatch-Waxman Act following Defendant's submission of ANDA No. 217353 and its subsequent notification to Plaintiff via a Paragraph IV certification letter, received around May 18, 2022, asserting that the patents-in-suit are invalid or would not be infringed by its proposed generic product. The patents are listed in the FDA's "Orange Book" with respect to GLYXAMBI®.

Case Timeline

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 describes the need for improved treatments for metabolic disorders such as type 1 and type 2 diabetes mellitus, impaired glucose tolerance, and hyperglycemia, noting the limitations of existing therapies (’957 Patent, col. 1:12-23).
• The Patented Solution: The invention is a pharmaceutical composition that combines two different classes of anti-diabetic drugs: a glucopyranosyl-substituted benzene derivative (an SGLT2 inhibitor) and a DPP IV inhibitor (’957 Patent, col. 1:24-34). This combination therapy aims to provide more effective glycemic control than monotherapy with either agent alone (’957 Patent, Abstract).
• Technical Importance: Combining anti-diabetic agents with different mechanisms of action was a key strategy to improve glycemic control and manage the progressive nature of type 2 diabetes (’957 Patent, col. 1:12-23).

Key Claims at a Glance

• The complaint asserts infringement of at least one claim (Compl. ¶27). Independent claim 1 is representative:
• A pharmaceutical composition comprising or made from:
  • a glucopyranosyl-substituted benzene derivative of formula (I) or a salt thereof, and
  • a DPP IV inhibitor of formula (II) or a salt thereof.

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

The Invention Explained

• Problem Addressed: The patent addresses the need for effective diabetes treatments for patients who also have renal impairment or chronic kidney disease (CKD). The use of many anti-diabetes agents is restricted in this patient population due to safety concerns or the need for dose reduction (’998 Patent, col. 1:27-46).
• The Patented Solution: The invention provides methods for treating type 2 diabetes by administering an SGLT-2 inhibitor, specifically empagliflozin, to patients with moderate renal impairment, a population for whom other treatments may be contraindicated or require adjustment (’998 Patent, col. 2:35-46, Abstract). The patent claims methods of use based on a patient's estimated glomerular filtration rate (eGFR), a measure of kidney function.
• Technical Importance: This technology provided a basis for using SGLT-2 inhibitors in a patient population with compromised kidney function, expanding the therapeutic options for these patients (’998 Patent, col. 1:42-46).

Key Claims at a Glance

• The complaint asserts infringement of at least one claim (Compl. ¶41). Independent claim 1 is representative:
• A method for improving glycemic control in a patient with type 2 diabetes mellitus and moderate renal impairment comprising:
  • administering empagliflozin to the patient,
  • wherein the patient has an estimated glomerular filtration rate (eGFR) of ≥30 ml/min/1.73 m² and <60 ml/min/1.73 m².

U.S. Patent No. 10,258,637 - "Pharmaceutical Composition, Method for Treating and Uses Thereof"

• Patent Identification: U.S. Patent No. 10,258,637, "Pharmaceutical Composition, Method for Treating and Uses Thereof," issued April 16, 2019 (Compl. ¶18).
• Technology Synopsis: The patent, which is in the same family as the ’998 Patent, relates to methods of treating type 2 diabetes in patients with specific stages of chronic kidney disease or renal impairment. It claims methods of administering empagliflozin to patients with an eGFR within a specified range to improve glycemic control (’637 Patent, Abstract; col. 1:27-46).
• Asserted Claims: The complaint alleges infringement of at least one claim of the patent (Compl. ¶55).
• Accused Features: The accused feature is the proposed generic drug product, which contains empagliflozin and is intended for the treatment of type 2 diabetes, allegedly as instructed on its proposed label (Compl. ¶¶52-53).

U.S. Patent No. 11,090,323 - "Pharmaceutical Composition, Methods for Treating and Uses Thereof"

• Patent Identification: U.S. Patent No. 11,090,323, "Pharmaceutical Composition, Methods for Treating and Uses Thereof," issued August 17, 2021 (Compl. ¶19).
• Technology Synopsis: This patent is also in the same family as the ’998 and ’637 Patents. It claims methods for treating type 2 diabetes in patients with renal impairment by administering empagliflozin, where treatment decisions (initiation and discontinuation) are tied to the patient's eGFR falling within or outside specific ranges (’323 Patent, Abstract; col. 1:27-46).
• Asserted Claims: The complaint alleges infringement of at least one claim of the patent (Compl. ¶69).
• Accused Features: The proposed generic empagliflozin-containing drug product and its intended use for treating type 2 diabetes, as will allegedly be described on its label, are the accused features (Compl. ¶¶66-67).

III. The Accused Instrumentality

Product Identification

• Defendant Ajanta Pharma Limited’s proposed generic empagliflozin and linagliptin tablets, in 10 mg/5 mg and 25 mg/5 mg dosages, for which Abbreviated New Drug Application (ANDA) No. 217353 was submitted to the FDA (Compl. ¶8).

Functionality and Market Context

• The accused products are generic versions of Plaintiffs’ GLYXAMBI® tablets (Compl. ¶1). The complaint alleges that the ANDA filing represents that the products demonstrate bioavailability or bioequivalence to GLYXAMBI® (Compl. ¶25). As such, the products are oral tablets designed to deliver a combination of empagliflozin, an SGLT2 inhibitor, and linagliptin, a DPP-IV inhibitor, for the management of type 2 diabetes (Compl. ¶¶1, 8). The filing of the ANDA signifies Defendant's intent to manufacture and sell these generic products in the United States prior to the expiration of the patents-in-suit (Compl. ¶26).

IV. Analysis of Infringement Allegations

The complaint alleges infringement under 35 U.S.C. § 271(e)(2), which defines the submission of an ANDA seeking approval to market a generic drug before patent expiration as an act of infringement. The complaint does not contain a detailed claim chart, but the infringement theory can be inferred from the nature of the accused product as a generic equivalent of GLYXAMBI®.

’957 Patent Infringement Allegations

’998 Patent Infringement Allegations

Identified Points of Contention

• Validity vs. Infringement: In Hatch-Waxman cases involving generic copies, the primary dispute is often over the validity of the patents rather than literal infringement. Defendant’s Paragraph IV letter alleges that the patents are invalid or will not be infringed (Compl. ¶26). This suggests that patent validity will be a central point of contention.
• Induced Infringement: For the method patents (’998, ’637, and ’323), a key question will be one of induced infringement. The analysis will focus on whether the contents of Defendant's proposed product label would instruct or encourage physicians and patients to use the generic drug in the specific manner claimed, particularly for the sub-population of patients with moderate renal impairment defined by specific eGFR values.

No probative visual evidence provided in complaint.

V. Key Claim Terms for Construction

"pharmaceutical composition" (’957 Patent, Claim 1)

• Context and Importance: This term defines the subject matter of the ’957 Patent. While seemingly straightforward, its construction could be critical if Defendant argues its formulation lacks certain characteristics implied by the specification, such as specific excipients, dosages, or release profiles, thereby attempting to design around the claim.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The claims broadly recite the two active ingredients without limitations on excipients, suggesting any formulation containing both could infringe (’957 Patent, col. 53:32-44).
  • Evidence for a Narrower Interpretation: The specification describes specific tablet formulations with particular excipients and manufacturing processes (’957 Patent, col. 51:4-52:67). A defendant could argue that these examples limit the scope of "pharmaceutical composition" to formulations with similar characteristics.

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

• Context and Importance: This term defines the purpose and outcome of the claimed method. The parties may dispute the degree of "improvement" required to meet this limitation. Practitioners may focus on this term because the efficacy of empagliflozin can be reduced in patients with renal impairment, raising the question of what constitutes a legally sufficient "improvement" in this specific patient population.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The patent suggests that "improving glycemic control" encompasses reducing fasting plasma glucose, postprandial plasma glucose, and/or glycosylated hemoglobin HbA1c, without specifying a minimum threshold of reduction (’998 Patent, col. 2:1-4).
  • Evidence for a Narrower Interpretation: The detailed description and clinical trial examples show specific, statistically significant reductions in HbA1c and other markers (’998 Patent, FIG. 1A). A defendant might argue that "improving" requires a clinically or statistically significant improvement similar to that disclosed in the patent's examples.

VI. Other Allegations

Indirect Infringement

• The complaint alleges both induced and contributory infringement for all four patents-in-suit. The inducement allegations are based on the assertion that Defendant's product labeling and package inserts will actively encourage and instruct physicians and patients to use the generic drug in an infringing manner (Compl. ¶¶33, 47, 61, 75). Contributory infringement is alleged on the basis that Defendant's product is especially made or adapted for an infringing use and is not a staple article of commerce suitable for substantial non-infringing use (Compl. ¶¶31, 45, 59, 73).

Willful Infringement

• The complaint does not use the term "willful," but it alleges that this is an "exceptional case" under 35 U.S.C. § 285, warranting an award of attorney fees (Compl. ¶¶36, 50, 64, 79). The basis for this allegation appears to be Defendant's filing of an ANDA with knowledge of the patents, as evidenced by its Paragraph IV certification letters sent to Plaintiff (Compl. ¶¶26, 40, 54, 68).

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

• A central issue will be patent validity: Given that the accused product is a generic equivalent, Defendant's primary defense, as indicated by its Paragraph IV certification, will likely focus on proving that the asserted claims of the four patents are invalid for reasons such as obviousness or lack of written description.
• A key evidentiary question will be one of induced infringement: For the method-of-use patents (’998, ’637, ’323), the case will likely turn on the specific language in Defendant's proposed product label. The court will need to determine if the label's instructions and indications for use would inevitably lead a significant number of patients, particularly those with moderate renal impairment, to be treated in a manner that directly infringes the patent claims.
• The dispute may also involve a question of claim scope: The definition of "improving glycemic control" in the context of renally impaired patients, where the drug's efficacy may be attenuated, could become a critical point of claim construction that determines whether the intended use of the generic product falls within the scope of the method claims.