DCT

1:24-cv-01091

Boehringer Ingelheim Pharma Inc v. Granules India Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-01091, D. Del., 09/30/2024
  • Venue Allegations: Venue is alleged to be proper on the basis that the defendant is a foreign corporation not residing in any U.S. district and may therefore be sued in any judicial district.
  • Core Dispute: Plaintiff alleges that Defendant's Abbreviated New Drug Application ("ANDA") to manufacture and sell a generic version of Plaintiff's JENTADUETO® tablets constitutes an act of infringement of five U.S. patents.
  • Technical Context: The technology concerns pharmaceutical compositions for treating type 2 diabetes, specifically stable formulations combining the DPP-IV inhibitor linagliptin with the antidiabetic agent metformin.
  • Key Procedural History: The litigation was triggered by Defendant's submission of ANDA No. 219778 and its subsequent Paragraph IV Certification letter, dated August 15, 2024, which asserted that the patents-in-suit are either invalid or will not be infringed by the proposed generic product. The complaint alleges that Defendant has refused to provide a copy of its ANDA under reasonable terms. It also alleges Defendant does not dispute infringement of the ’388 patent and does not assert invalidity of the ’705, ’016, ’379, or ’827 patents, suggesting the dispute for those patents may center on non-infringement and invalidity, respectively.

Case Timeline

Date Event
2008-04-03 Priority Date for ’705, ’016, ’379, and ’827 Patents
2008-10-16 Priority Date for ’388 Patent
2015-10-13 U.S. Patent No. 9,155,705 Issues
2016-08-16 U.S. Patent No. 9,415,016 Issues
2018-07-17 U.S. Patent No. 10,022,379 Issues
2021-04-13 U.S. Patent No. 10,973,827 Issues
2024-02-27 U.S. Patent No. 11,911,388 Issues
2024-08-15 Plaintiff receives Paragraph IV Certification letter from Defendant
2024-09-30 Complaint Filed

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

U.S. Patent No. 9,155,705 - "DPP-IV Inhibitor Combined With A Further Antidiabetic Agent, Tablets Comprising Such Formulations, Their Use And Process For Their Preparation," Issued October 13, 2015

The Invention Explained

  • Problem Addressed: The patent addresses chemical incompatibilities that arise when combining certain DPP-4 inhibitors, which have a primary or secondary amino group, with other drugs or common pharmaceutical excipients (U.S. Patent No. 10,022,379 B2, col. 5:6-24). These incompatibilities can lead to degradation of the active pharmaceutical ingredient, affecting the stability and efficacy of the final drug product (U.S. Patent No. 10,022,379 B2, col. 5:41-51).
  • The Patented Solution: The invention provides a stable fixed-dose combination by incorporating a nucleophilic and/or basic agent, such as the amino acid L-arginine, into the formulation (U.S. Patent No. 10,022,379 B2, col. 5:36-44). This agent acts as a stabilizer, suppressing the degradation of the DPP-4 inhibitor when it is combined with a partner drug like metformin (U.S. Patent No. 10,022,379 B2, col. 6:1-3; col. 14:49-60).
  • Technical Importance: This approach allows for the creation of a stable, oral solid dosage form that combines two different types of antidiabetic agents, potentially improving patient compliance by reducing the number of pills a patient must take (U.S. Patent No. 10,022,379 B2, col. 1:10-14).

Key Claims at a Glance

  • The complaint asserts at least one claim, citing independent claim 1 as representative (Compl. ¶30).
  • The essential elements of independent claim 1 are:
    • A solid pharmaceutical composition comprising or made from:
    • (a) 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine (linagliptin) in a dosage range from about 0.5 mg to about 10 mg,
    • (b) metformin hydrochloride,
    • (c) a pharmaceutical excipient, and
    • (d) about 1 mg to 50 mg of L-arginine.

U.S. Patent No. 9,415,016 - "DPP-IV Inhibitor Combined With A Further Antidiabetic Agent, Tablets Comprising Such Formulations, Their Use And Process For Their Preparation," Issued August 16, 2016

The Invention Explained

  • Problem Addressed: As with the ’705 Patent, this patent addresses the chemical instability and degradation of DPP-4 inhibitors when formulated in combination with metformin (U.S. Patent No. 10,022,379 B2, col. 5:6-24).
  • The Patented Solution: The invention claims a specific tablet formulation containing linagliptin and metformin hydrochloride, stabilized by a "basic amino acid" present in an "amount sufficient to suppress degradation" of the linagliptin (U.S. Patent No. 10,973,827 B2, col. 13:49-60). The claim specifies dosage amounts and percentage weights for the components within a film-coated tablet (U.S. Patent No. 10,973,827 B2, Claim 1).
  • Technical Importance: This solution provides a specific, quantified formulation for a stable combination tablet, offering a precise recipe for manufacturing a dual-action oral antidiabetic medication (U.S. Patent No. 10,022,379 B2, col. 1:10-14).

Key Claims at a Glance

  • The complaint asserts at least one claim, citing independent claim 1 as representative (Compl. ¶31).

  • The essential elements of independent claim 1 are:

    • A pharmaceutical composition comprising or made from:
    • (a) linagliptin in a dosage of 2.5 mg or 5 mg,
    • (b) metformin hydrochloride,
    • (c) one or more pharmaceutical excipients, and
    • (d) a basic amino acid present in an amount sufficient to suppress degradation of the linagliptin,
    • wherein the composition is a film-coated tablet comprising specific weight percentages of linagliptin (0.1-0.5%) and metformin hydrochloride (47-85%).

  • Patent Identification: U.S. Patent No. 10,022,379, "DPP-IV Inhibitor Combined With A Further Antidiabetic Agent, Tablets Comprising Such Formulations, Their Use And Process For Their Preparation," Issued July 17, 2018.

  • Technology Synopsis: This patent claims a method of treating type 2 diabetes by administering a pharmaceutical composition similar to that described in the ’016 Patent (Compl. ¶32). The claims specify the active ingredients (linagliptin and metformin), the form (film-coated tablet), and the weight percentages of the components, including the stabilizing basic amino acid (U.S. Patent No. 10,022,379 B2, Claim 1).

  • Asserted Claims: At least one claim is asserted, with independent claim 1 cited as representative (Compl. ¶32, ¶61).

  • Accused Features: Defendant's proposed generic product, if manufactured and used as directed for the treatment of type 2 diabetes, is alleged to infringe this method patent (Compl. ¶¶61, 64).

  • Patent Identification: U.S. Patent No. 10,973,827, "DPP-IV Inhibitor Combined With A Further Antidiabetic Agent, Tablets Comprising Such Formulations, Their Use And Process For Their Preparation," Issued April 13, 2021.

  • Technology Synopsis: This patent claims a more detailed pharmaceutical composition than the earlier patents. It specifies not only the active ingredients and stabilizing agent (L-arginine) but also precise percentage ranges for additional excipients such as a binder, fillers, a lubricant, and a glidant within a film-coated tablet (Compl. ¶33). This level of detail further defines the specific recipe for a stable combination drug product (U.S. Patent No. 10,973,827 B2, Claim 1).

  • Asserted Claims: At least one claim is asserted, with independent claim 1 cited as representative (Compl. ¶33, ¶72).

  • Accused Features: Defendant's proposed generic tablet is alleged to be a pharmaceutical composition that contains the specific combination of active ingredients and excipients in the claimed percentage ranges (Compl. ¶72).

  • Patent Identification: U.S. Patent No. 11,911,388, "Treatment For Diabetes In Patients With Insufficient Glycemic Control Despite Therapy With An Oral Or Non-Oral Antidiabetic Drug," Issued February 27, 2024.

  • Technology Synopsis: This patent claims a method of treating a specific patient population: type 2 diabetes patients who have renal impairment and insufficient glycemic control despite existing metformin therapy (Compl. ¶34). The claimed method comprises administering a DPP-4 inhibitor (linagliptin) at a specific oral daily amount of 5 mg (U.S. Patent No. 11,911,388 B2, Claim 1).

  • Asserted Claims: At least one claim is asserted, with independent claim 1 cited as representative (Compl. ¶34, ¶83).

  • Accused Features: Defendant's proposed generic product, via its product labeling and instructions, will allegedly direct healthcare providers and patients to use the product in a manner that infringes this method, particularly for the specified patient population (Compl. ¶83, ¶86). The complaint alleges that Granules does not dispute that its product will infringe the claims of this patent (Compl. ¶28, ¶91).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality is Granules' proposed generic linagliptin and metformin hydrochloride tablets in 2.5/500 mg, 2.5/850 mg, and 2.5/1000 mg strengths, for which ANDA No. 219778 was submitted to the FDA (the "Granules ANDA Product") (Compl. ¶9).
  • Functionality and Market Context: The Granules ANDA Product is intended to be a generic version of Boehringer's JENTADUETO® tablets (Compl. ¶1). The ANDA filing contains data intended to demonstrate the bioequivalence of the Granules ANDA Product to JENTADUETO® (Compl. ¶26). Upon approval, Granules intends to commercially manufacture, market, and sell the product in the United States as a lower-cost generic alternative to the branded drug (Compl. ¶10). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide sufficient detail to populate a claim chart comparing the elements of the asserted patents to specific features of the accused product. This is because the complaint alleges that Boehringer has not been granted access to Granules' confidential ANDA submission (Compl. ¶¶36-37). The infringement allegations are therefore based on information and belief that the product described in the ANDA, if approved and commercialized, will meet the limitations of the asserted claims.

The core infringement theory for the composition patents (’705, ’016, and ’827) is that for Granules' product to be bioequivalent to JENTADUETO®, it must necessarily be a solid pharmaceutical composition comprising linagliptin, metformin hydrochloride, and a stabilizing agent like L-arginine, thereby meeting the elements of the asserted claims (Compl. ¶¶39, 50, 72). For the method patents (’379 and ’388), the theory is that the proposed product label will instruct users to administer the drug in a way that directly infringes the claimed methods of treatment (Compl. ¶¶64, 86).

  • Identified Points of Contention:
    • Factual Questions: A central question will be whether the specific formulation detailed in Granules' confidential ANDA actually contains every element of the asserted composition claims. For instance, does it use L-arginine as required by claim 1 of the ’705 Patent, or another "basic amino acid" as recited in claim 1 of the ’016 Patent? Does the formulation meet the specific weight percentage limitations required by claims in the ’016 and ’827 Patents?
    • Scope Questions: The dispute may raise the question of whether any alternative stabilizer used by Granules, if not L-arginine, falls within the scope of the term "a basic amino acid having an intramolecular amino group and alkaline characteristics" (’016 Patent, claim 1; Compl. ¶31). Another question is whether Granules' stabilizer is present in an "amount sufficient to suppress degradation" of the linagliptin, which is a functional limitation that will require evidentiary support and may be a focus of claim construction.

V. Key Claim Terms for Construction

’705 Patent, Claim 1

  • The Term: "comprising or made from"
  • Context and Importance: This transitional phrase defines the relationship between the preamble ("A solid pharmaceutical composition") and the body of the claim listing the components. Whether the claim is interpreted as "comprising" (open-ended, allowing additional, unlisted ingredients) or "made from" (potentially more limiting, focusing on the essential starting materials) could be critical if Granules' formulation includes additional stabilizers or excipients not listed in claim 1.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The use of the open-ended term "comprising" is standard patent practice to signify that the invention includes the listed elements but does not exclude others. The specification describes various excipients that may be used, suggesting the four listed ingredients are not an exhaustive list (U.S. Patent No. 10,022,379 B2, col. 6:52-67).
    • Evidence for a Narrower Interpretation: The alternative phrase "or made from" could be argued to limit the claim to compositions whose essential character is defined by the four listed components, potentially excluding formulations where an unlisted ingredient materially alters the composition's properties.

’016 Patent, Claim 1

  • The Term: "an amount sufficient to suppress degradation"
  • Context and Importance: This is a functional limitation that defines the required quantity of the "basic amino acid." Practitioners may focus on this term because infringement will depend not just on the presence of a basic amino acid, but on demonstrating that it is present in a quantity that achieves a specific technical result (stabilization). This raises an evidentiary question about how much degradation is suppressed and what level of suppression is "sufficient."
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent specification describes L-arginine as having a "particular suitable stabilizing effect" and notes that its use allows for "protection against decomposition and degradation" (U.S. Patent No. 10,022,379 B2, col. 6:26-29; col. 5:48-51). This language could support a broad reading where any scientifically measurable suppression of degradation is "sufficient."
    • Evidence for a Narrower Interpretation: The patent provides specific examples of formulations with defined amounts of L-arginine (e.g., 12.5 mg, 21.2 mg, 25 mg) that were shown to be stable (U.S. Patent No. 10,022,379 B2, Table 1, col. 22:1-40). A party might argue that the "sufficient amount" must be within or analogous to the ranges proven effective in the patent's own examples.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement for all five patents. For the composition patents, inducement is based on the allegation that Granules' package inserts will instruct users to use the product, which itself constitutes direct infringement (Compl. ¶47, ¶57, ¶79). For the method of use patents, inducement is alleged based on product labeling that will instruct users to take the drug for the claimed therapeutic purpose (Compl. ¶68, ¶90). Contributory infringement is alleged on the basis that the Granules ANDA Product has no substantial non-infringing uses (Compl. ¶44, ¶55, ¶66, ¶77, ¶88).

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

  • A central issue will be one of compositional identity: Once the formulation in Granules' confidential ANDA is disclosed in discovery, the primary question will be whether it contains the precise combination of ingredients, including a stabilizing "basic amino acid" like L-arginine, and meets the specific dosage and weight-percentage limitations recited in the asserted composition patents (’705, ’016, ’827). Any deviation will shift the focus to claim construction and the doctrine of equivalents.
  • A key strategic question will be the division of infringement and validity challenges: The complaint suggests a strategic split, with Granules' defense for the four composition/formulation patents (’705, ’016, ’379, ’827) resting on non-infringement, while its defense for the ’388 method-of-use patent rests on invalidity. The case will likely bifurcate along these lines, with discovery and expert testimony focused on dissecting the accused product's formulation for the former, and on prior art for the latter.
  • An early procedural question will be one of pleading sufficiency: Given that Boehringer has not seen the ANDA, the court may need to address whether the infringement allegations, made on "information and belief" that the generic must be the same as the branded product to be bioequivalent, are plausible enough to proceed to discovery, where the actual composition of the accused product will be revealed.