DCT
1:19-md-02902
In re: Sitagliptin Phosphate ('708 & '921) Patent Litigation
Key Events
Amended Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Merck Sharp & Dohme Corp. (New Jersey)
- Defendant: Aurobindo Pharma Limited (India) and Aurobindo Pharma USA, Inc. (Delaware)
- Plaintiff’s Counsel: McCarter & English, LLP; Williams & Connolly LLP
- Case Identification: 1:19-md-02902, D. Del., 02/17/2021
- Venue Allegations: Venue is alleged to be proper based on Defendant Aurobindo Pharma USA, Inc. being a Delaware corporation that has consented to jurisdiction, and its parent, Aurobindo Pharma, Ltd., having purposefully availed itself of Delaware's laws through its subsidiary's systematic business contacts and regular participation in patent litigation within the district.
- Core Dispute: Plaintiff alleges that Defendants’ submission of an Abbreviated New Drug Application (ANDA) to market a generic version of the diabetes drug JANUMET® constitutes an act of infringement of two patents covering the drug's active ingredient and its formulation.
- Technical Context: The technology involves pharmaceutical chemistry, specifically a stable salt form of the DPP-4 inhibitor sitagliptin and a fixed-dose combination oral tablet of sitagliptin and metformin for the treatment of Type 2 diabetes.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following a notice letter from Aurobindo, dated July 10, 2020, which informed Merck of its ANDA filing containing a Paragraph IV certification against the patents-in-suit. A Paragraph IV certification asserts that the listed patents are invalid, unenforceable, and/or will not be infringed by the generic product. The case is part of a multi-district litigation concerning these patents, which are listed in the FDA's Orange Book for JANUMET®.
Case Timeline
| Date | Event |
|---|---|
| 2003-06-24 | U.S. Patent 7,326,708 Priority Date |
| 2005-12-16 | U.S. Patent 8,414,921 Priority Date |
| 2008-02-05 | U.S. Patent 7,326,708 Issue Date |
| 2013-04-09 | U.S. Patent 8,414,921 Issue Date |
| 2020-07-10 | Aurobindo sends Notice Letter to Merck regarding ANDA submission |
| 2021-02-17 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,326,708 - "Phosphoric Acid Salt of a Dipeptidyl Peptidase-IV Inhibitor", issued February 5, 2008
The Invention Explained
- Problem Addressed: The patent background identifies inhibition of the dipeptidyl peptidase-IV (DP-IV) enzyme as a novel approach for treating Type 2 diabetes (’708 Patent, col. 1:31-40). While a specific DP-IV inhibitor compound (sitagliptin) was known, the patent notes a need for a form of the compound with improved properties for pharmaceutical manufacturing, such as enhanced stability, ease of processing, and handling ('708 Patent, col. 2:5-15).
- The Patented Solution: The invention is a specific salt form of sitagliptin: the dihydrogenphosphate salt. This salt, particularly in its crystalline monohydrate form, is described as possessing improved physical and chemical stability and better physicochemical properties (e.g., solubility) compared to other forms ('708 Patent, col. 2:5-15, Abstract). These characteristics make it particularly suitable for manufacturing consistent and stable pharmaceutical dosage forms ('708 Patent, col. 2:50-65). Figure 1 of the patent provides a characteristic X-ray diffraction pattern to identify the specific crystalline structure ('708 Patent, col. 2:23-26).
- Technical Importance: Creating a stable, crystalline salt of an active pharmaceutical ingredient is a critical step in drug development, as it directly impacts the drug's manufacturability, shelf life, and bioavailability ('708 Patent, col. 2:5-15).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 (Compl. ¶35).
- Claim 1 Elements:
- A dihydrogenphosphate salt of 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine of structural formula I
- or a hydrate thereof.
U.S. Patent No. 8,414,921 - "Pharmaceutical Compositions of Combinations of Dipeptidyl Peptidase-4 Inhibitors with Metformin", issued April 9, 2013
The Invention Explained
- Problem Addressed: The patent explains that long-term treatment of Type 2 diabetes often requires combination therapy. However, prescribing multiple individual pills can be complex and burdensome for patients, potentially reducing compliance (’921 Patent, col. 1:17-30). The technical challenge is to create a single, stable, fixed-dose tablet that effectively combines two different active ingredients.
- The Patented Solution: The invention is a specific pharmaceutical formulation for an immediate-release tablet that combines sitagliptin (or a salt thereof) with metformin hydrochloride ('921 Patent, col. 3:5-7). The patent claims a composition defined by specific weight percentage ranges for the two active ingredients as well as for several categories of excipients: a lubricant, a binding agent, a surfactant, and a diluent ('921 Patent, col. 42:47-67, Abstract).
- Technical Importance: Developing a successful fixed-dose combination product is a significant pharmaceutical formulation challenge, requiring careful selection of excipients to ensure drug stability, prevent negative interactions between components, and achieve the desired immediate-release profile for both active ingredients ('921 Patent, col. 1:17-30).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 (Compl. ¶54).
- Claim 1 Elements:
- A pharmaceutical composition comprising:
- (a) about 3 to 20% by weight of sitagliptin, or a pharmaceutically acceptable salt thereof;
- (b) about 25 to 94% by weight of metformin hydrochloride;
- (c) about 0.1 to 10% by weight of a lubricant;
- (d) about 0 to 35% by weight of a binding agent;
- (e) about 0.5 to 1% by weight of a surfactant; and
- (f) about 5 to 15% by weight of a diluent.
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is "Aurobindo's ANDA Product," identified as a generic version of Merck's JANUMET® comprising "sitagliptin phosphate; metformin hydrochloride oral tablets" (Compl. ¶¶1-3).
Functionality and Market Context
- The product is an oral tablet intended for the treatment of Type 2 diabetes (Compl. ¶1). It contains two active pharmaceutical ingredients, sitagliptin phosphate and metformin hydrochloride (Compl. ¶¶34, 54). The complaint alleges that Aurobindo seeks to manufacture and sell this product in the U.S. before the expiration of the patents-in-suit, with the filing of its ANDA constituting the act of infringement under the Hatch-Waxman Act (Compl. ¶¶37, 55).
- No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
U.S. Patent 7,326,708 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A dihydrogenphosphate salt of 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine...or a hydrate thereof. | Aurobindo's ANDA Product contains sitagliptin phosphate as an active ingredient, which the complaint alleges is covered by claim 1. | ¶34, ¶35 | col. 2:44-51 |
- Identified Points of Contention:
- The complaint alleges that in its notice letter, "Aurobindo did not contest infringement of claim 1 of the '708 patent" (Compl. ¶36). This strongly suggests that the primary legal battle over this patent will not concern non-infringement but will instead focus on the invalidity and/or unenforceability defenses asserted in Aurobindo's Paragraph IV certification (Compl. ¶33).
U.S. Patent 8,414,921 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| (a) about 3 to 20% by weight of sitagliptin, or a pharmaceutically acceptable salt thereof | The composition of Aurobindo's ANDA Product is alleged to include sitagliptin phosphate in the same or equivalent amount as the claimed range. | ¶54 | col. 3:56-61 |
| (b) about 25 to 94% by weight of metformin hydrochloride | The composition of Aurobindo's ANDA Product is alleged to include metformin hydrochloride in the same or equivalent amount as the claimed range. | ¶54 | col. 3:56-61 |
| (c) about 0.1 to 10% by weight of a lubricant | The composition of Aurobindo's ANDA Product is alleged to include a lubricant in the same or equivalent amount as the claimed range. | ¶54 | col. 5:5-10 |
| (d) about 0 to 35% by weight of a binding agent | The composition of Aurobindo's ANDA Product is alleged to include a binding agent in the same or equivalent amount as the claimed range. | ¶54 | col. 5:11-18 |
| (e) about 0.5 to 1% by weight of a surfactant | The composition of Aurobindo's ANDA Product is alleged to include a surfactant in the same or equivalent amount as the claimed range. | ¶54 | col. 5:37-48 |
| (f) about 5 to 15% by weight of a diluent | The composition of Aurobindo's ANDA Product is alleged to include a diluent in the same or equivalent amount as the claimed range. | ¶54 | col. 5:20-27 |
- Identified Points of Contention:
- Technical Questions: A key question will be whether the specific formulation in Aurobindo's ANDA, which is confidential, factually meets every weight-percentage limitation of claim 1. The complaint’s use of "same or equivalent" language suggests a potential dispute over literal infringement versus infringement under the doctrine of equivalents (Compl. ¶54).
- Scope Questions: The interpretation of the term "about," which qualifies every numerical range in claim 1, will be critical. The dispute may turn on how much numerical variance from the recited percentages is permitted by the term "about."
V. Key Claim Terms for Construction
- The Term: "about" (from '921 Patent, claim 1)
- Context and Importance: This term governs the scope of all six quantitative limitations in claim 1 of the ’921 Patent. The infringement analysis will depend entirely on whether the weight percentages of the components in Aurobindo's product fall within the boundaries defined by "about." Practitioners may focus on this term because even minor differences between Aurobindo's formulation and the claimed ranges could be dispositive of literal infringement.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent consistently uses "about" for every range in the claim, suggesting the patentee did not intend to be limited to the precise numerical values and foresaw some level of variability inherent in pharmaceutical manufacturing ('921 Patent, col. 42:47-67).
- Evidence for a Narrower Interpretation: The specification includes multiple examples with highly specific component weights, such as "64.25 mg" of sitagliptin phosphate monohydrate and "500 mg" of metformin hydrochloride ('921 Patent, col. 9:11-12, Example 1). A party could argue that "about" should be construed narrowly in light of these precise examples and should not be read to encompass formulations that differ significantly from them.
VI. Other Allegations
- Indirect Infringement: The complaint alleges both active inducement and contributory infringement for both patents. The inducement claims are based on the allegation that Aurobindo's proposed product labeling will instruct physicians and patients to use the drug in an infringing manner (Compl. ¶¶41, 59). Contributory infringement is alleged on the basis that the accused product is not a staple article of commerce and is especially made for an infringing use (Compl. ¶¶42, 60).
- Willful Infringement: Willfulness is alleged based on Aurobindo’s pre-suit knowledge of the patents, evidenced by its Paragraph IV certification and notice letter (Compl. ¶¶43, 45, 62, 64). The complaint asserts that despite this knowledge, Aurobindo has persisted in its intent to market the infringing product.
VII. Analyst’s Conclusion: Key Questions for the Case
- Patent Validity: Given that Aurobindo filed a Paragraph IV certification alleging invalidity and did not contest infringement of the '708 patent, a central question for the court will be one of patent validity: Can Aurobindo meet its burden of proving by clear and convincing evidence that the asserted claims of the '708 and/or '921 patents are invalid, for example, on grounds of obviousness or lack of adequate written description?
- Compositional Scope: For the '921 patent, the case will likely involve a key question of definitional scope and factual comparison: How will the court construe the term "about," and does the specific formulation detailed in Aurobindo's confidential ANDA fall within the scope of the claim's six weight-percentage limitations, either literally or under the doctrine of equivalents?