DCT
1:24-cv-00545
Merck Sharp & Dohme LLC v. Azurity Pharma Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Merck Sharp & Dohme LLC. (New Jersey)
- Defendant: Azurity Pharmaceuticals, Inc. (Delaware)
- Plaintiff’s Counsel: McCarter & English, LLP
- Case Identification: 1:24-cv-00545, D. Del., 05/03/2024
- Venue Allegations: Venue is asserted as proper because the Defendant is a corporation organized and existing under the laws of Delaware.
- Core Dispute: Plaintiff alleges that Defendant’s submission of a New Drug Application to the FDA for a generic sitagliptin oral solution constitutes an act of infringement of a patent covering a specific salt form of that active ingredient.
- Technical Context: The technology concerns a specific phosphate salt of sitagliptin, a dipeptidyl peptidase-IV (DPP-IV) inhibitor marketed by Merck as JANUVIA® for the treatment of Type 2 diabetes.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following a notice letter from the Defendant, dated March 19, 2024, which included a Paragraph IV certification asserting that the patent-in-suit is invalid, unenforceable, or will not be infringed by the proposed generic product. The patent-in-suit, U.S. Patent No. 7,326,708, was the subject of several inter partes review (IPR) proceedings, which concluded with a certificate issued on September 19, 2023, confirming the patentability of claims 1-4, 17, 19, and 21-23.
Case Timeline
| Date | Event |
|---|---|
| 2003-06-24 | '708 Patent Priority Date |
| 2008-02-05 | '708 Patent Issue Date |
| 2023-09-19 | IPR Certificate Issued for '708 Patent |
| 2024-03-19 | Defendant's Notice Letter to Plaintiff |
| 2024-05-03 | 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
The Invention Explained
- Problem Addressed: The patent acknowledges the prior disclosure of the active compound, sitagliptin, as a potent inhibitor of the DPP-IV enzyme for treating Type 2 diabetes (ʼ708 Patent, col. 1:49-58). The implicit technical challenge addressed is the need to develop a form of this compound with properties suitable for a pharmaceutical product, such as chemical and physical stability, and ease of manufacturing ('708 Patent, col. 2:5-18).
- The Patented Solution: The invention is a specific salt of sitagliptin: the dihydrogenphosphate salt. The patent describes this salt and its crystalline hydrates as having advantageous properties, including improved stability and solubility, which render it "particularly suitable for the manufacture of various pharmaceutical dosage forms" ('708 Patent, col. 2:12-18, Abstract). The specification provides a detailed description of a crystalline monohydrate form of this salt ('708 Patent, col. 2:63-65, Fig. 1).
- Technical Importance: The creation of a specific, stable, and manufacturable salt form is a critical step in transforming a promising chemical compound into a viable and effective drug product ('708 Patent, col. 2:5-18).
Key Claims at a Glance
- The complaint asserts infringement of one or more claims, including independent claim 1 (Compl. ¶22).
- Independent Claim 1:
- 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.
- The complaint does not explicitly reserve the right to assert dependent claims but makes a general allegation of infringement of "one or more claims" (Compl. ¶30).
III. The Accused Instrumentality
Product Identification
The accused instrumentality is Defendant Azurity's proposed generic sitagliptin oral solution, which is the subject of New Drug Application ("NDA") No. 219122 submitted to the FDA (Compl. ¶¶ 1-2).
Functionality and Market Context
The complaint alleges that Azurity’s NDA Product contains sitagliptin as an active ingredient and is a generic version of Merck's JANUVIA® product (Compl. ¶¶ 3, 26). The action is filed under 35 U.S.C. § 271(e)(2), which defines the submission of such an application for the purpose of obtaining approval to market a drug claimed in a patent before its expiration as an act of infringement (Compl. ¶31). The complaint notes that Merck has not yet received Azurity's NDA or Drug Master File (DMF) and that the parties were unable to agree to terms for access (Compl. ¶28).
IV. Analysis of Infringement Allegations
The complaint does not provide a detailed claim chart or specific technical information about the accused product's composition, stating that such information is contained in confidential documents not yet produced by the Defendant (Compl. ¶28). The infringement theory is based on the allegation that Azurity seeks to market a generic version of JANUVIA®, which is covered by the '708 patent (Compl. ¶¶ 3, 22).
'708 Patent 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 of structural formula I, or a hydrate thereof. | On information and belief, Azurity’s NDA Product, which contains sitagliptin, is or contains the claimed dihydrogenphosphate salt of sitagliptin or a hydrate thereof, thereby falling within the scope of one or more claims of the patent. | ¶¶ 26, 30 | col. 14:62-67 |
- Identified Points of Contention:
- Factual Question: The central issue is factual: what is the precise chemical composition and crystalline form of the active pharmaceutical ingredient in Azurity’s proposed product? The complaint is filed on the "good faith belief" of infringement, but acknowledges a lack of direct evidence pending discovery of Azurity's confidential FDA filings (Compl. ¶¶ 28-29).
- Scope Questions: The dispute may turn on the scope of the claims. Does Azurity's product contain the specific "dihydrogenphosphate salt" recited in Claim 1? If not, does it contain a different salt form of sitagliptin that falls outside the claim scope? Further, the interpretation of "or a hydrate thereof" could become significant depending on the hydration state of Azurity's product.
No probative visual evidence provided in complaint.
V. Key Claim Terms for Construction
The complaint does not provide sufficient detail for analysis of specific claim construction disputes. However, based on the patent and the nature of the case, the following terms may be central.
The Term: "a dihydrogenphosphate salt"
- Context and Importance: This term defines the specific counter-ion complexed with the sitagliptin active moiety. The infringement analysis will depend entirely on whether Azurity's product is, in fact, this particular salt. Practitioners may focus on this term because non-infringement could be established if Azurity uses a different, non-claimed salt of sitagliptin.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claims are not limited to a specific crystalline form, which may suggest that any form of the dihydrogenphosphate salt (amorphous or crystalline) is covered.
- Evidence for a Narrower Interpretation: The specification defines the salt as comprised of "one molar equivalent of mono-protonated...cation and one molar equivalent of dihydrogenphosphate (biphosphate) anion" ('708 Patent, col. 4:32-38). An argument could be made that the claims are limited to this specific 1:1 molar ratio.
The Term: "or a hydrate thereof"
- Context and Importance: This term provides an alternative to the anhydrous salt. Its interpretation will be critical if Azurity's product is a solvate other than a hydrate, or an anhydrous form that differs from the one described in the patent.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The use of "a" and "or" suggests the claim covers the dihydrogenphosphate salt in either its anhydrous form or any of its hydrated forms.
- Evidence for a Narrower Interpretation: The specification heavily emphasizes a specific "crystalline monohydrate" ('708 Patent, col. 4:56-57; Fig. 1-5). A party could argue that "a hydrate thereof" should be interpreted in light of these specific disclosures, potentially limiting the scope to this monohydrate form.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Azurity will actively induce infringement by directing the use of its product through its proposed labeling, and that Azurity has specific intent to do so (Compl. ¶¶ 34-35). It further alleges contributory infringement, stating the product is not a staple article of commerce and is especially made for an infringing use (Compl. ¶36).
- Willful Infringement: Willfulness is alleged based on Azurity’s purported "full knowledge of the '708 patent and without a reasonable basis for believing that it would not be liable for infringement" (Compl. ¶39). This knowledge is predicated on Azurity's submission of the Paragraph IV certification.
VII. Analyst’s Conclusion: Key Questions for the Case
Given that the asserted claims were recently confirmed as patentable in IPR proceedings, the case will likely center on infringement rather than validity. The primary questions for the court appear to be:
- A core issue will be one of chemical identity: Does Azurity's proposed generic product, as described in its confidential NDA, contain the specific "dihydrogenphosphate salt" of sitagliptin as recited in Claim 1, or a different salt form?
- A key evidentiary question will be one of physical form: If Azurity's product does contain the claimed salt, does its specific physical state (e.g., crystalline, amorphous, hydration level) fall within the scope of the asserted claims, particularly the phrase "or a hydrate thereof"?
- A secondary issue may concern inducement: Assuming direct infringement is found, does Azurity’s proposed product label contain instructions that teach an infringing use, thereby satisfying the requirements for induced infringement?