DCT
1:19-cv-00312
Merck Sharp & Dohme Corp v. Sandoz Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Merck Sharp & Dohme Corp. (New Jersey)
- Defendant: Sandoz Inc. (Colorado)
- Plaintiff’s Counsel: McCarter & English, LLP
- Case Identification: 1:19-cv-00312, D. Del., 02/13/2019
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Sandoz is subject to personal jurisdiction, has previously consented to venue in the district, and conducts substantial business in the state, including the marketing and sale of generic drugs.
- Core Dispute: Plaintiff alleges that Defendant’s submission of Abbreviated New Drug Applications (ANDAs) to market generic versions of the diabetes drugs JANUVIA® and JANUMET® constitutes an act of infringement of a patent claiming a specific phosphate salt form of the active ingredient, sitagliptin.
- Technical Context: The technology concerns a specific, stable salt form of a Dipeptidyl Peptidase-IV (DP-IV) inhibitor, an active pharmaceutical ingredient (API) used to treat Type 2 diabetes, which possesses advantageous properties for manufacturing and formulation.
- Key Procedural History: This Hatch-Waxman litigation was initiated in response to notice letters, dated December 20, 2010, in which Sandoz informed Merck of its ANDA submissions containing Paragraph IV certifications. These certifications asserted that U.S. Patent No. 7,326,708 is invalid, unenforceable, and/or would not be infringed by Sandoz's proposed generic products. Subsequent to the filing of this complaint, the asserted patent was the subject of Inter Partes Review proceedings (IPR2020-00040, IPR2020-01060, IPR2020-01072), which concluded with a certificate issued 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 |
| 2010-12-20 | Sandoz sends Notice Letters to Merck regarding ANDA filings |
| 2019-02-13 | Complaint Filing Date |
| 2023-09-19 | IPR Certificate issued confirming patentability of asserted claims |
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’s background section notes that while the base chemical compound (sitagliptin) was a known DP-IV inhibitor for treating Type 2 diabetes, there was no specific disclosure of a salt form suitable for pharmaceutical development (’708 Patent, col. 1:50-63). Developing a stable, manufacturable solid dosage form requires an active ingredient with optimal physical and chemical properties.
- The Patented Solution: The invention is a specific dihydrogenphosphate salt of sitagliptin. This salt form is described as having advantages for preparing pharmaceutical compositions, including "improved physical and chemical stability," better solubility, and "ease of processing, handling, and dosing" (’708 Patent, col. 2:5-16). The specification places particular emphasis on a "crystalline monohydrate" of this salt, providing detailed characterization data for it (’708 Patent, col. 2:3-4; Figs. 1-5).
- Technical Importance: The creation of a specific, stable, and highly pure salt form is a critical step in transforming a promising chemical compound into a reliable and mass-producible pharmaceutical product (’708 Patent, col. 2:5-16).
Key Claims at a Glance
- The complaint asserts at least independent claim 1 (Compl. ¶33, ¶53).
- The essential elements of independent claim 1 are:
- 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’s prayer for relief seeks a judgment that the ’708 patent has been infringed, which could encompass other claims not explicitly detailed in the initial pleading (Compl. p. 12-13).
III. The Accused Instrumentality
- Product Identification: The accused instrumentalities are Sandoz’s proposed generic drug products identified in ANDA No. 202387 ("Sandoz's '387 ANDA Product") and ANDA No. 202388 ("Sandoz's '388 ANDA Product") (Compl. ¶¶ 2, 4).
- Functionality and Market Context: The complaint alleges that Sandoz’s products are generic versions of Merck’s branded drugs, JANUVIA® (sitagliptin phosphate) and JANUMET® (metformin hydrochloride; sitagliptin phosphate) (Compl. ¶¶ 3, 5). The key technical feature identified in the complaint is that both of Sandoz's proposed products contain "sitagliptin phosphate as an active ingredient" (Compl. ¶32, ¶52).
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
- Claim Chart Summary: The complaint does not contain a formal claim chart. The infringement theory is summarized below based on the complaint's narrative allegations.
'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... | Sandoz’s ANDA products are alleged to contain "sitagliptin phosphate as an active ingredient." The complaint further alleges that Claim 1 "covers the sitagliptin phosphate" in Sandoz's products. | ¶32, ¶33, ¶52, ¶53 | col. 2:44-52 |
| ...or a hydrate thereof. | The complaint alleges infringement of Claim 1, which covers both anhydrous and hydrated forms of the salt. The allegation that the product contains "sitagliptin phosphate" is asserted to meet the claim limitation. | ¶33, ¶53 | col. 16:15-18 |
- Identified Points of Contention:
- Technical Questions: A primary technical question will be the precise molecular structure and crystalline form (polymorph) of the "sitagliptin phosphate" API in Sandoz's ANDA products. The complaint does not provide this level of detail, but it will be a central focus of discovery. The dispute may turn on whether Sandoz has developed a different polymorph or an amorphous form that it argues falls outside the scope of the claims.
- Scope Questions: This raises the question of whether "covers," as used in the complaint, alleges literal infringement. The key legal dispute will likely be whether the specific form of sitagliptin phosphate in Sandoz's ANDAs is the same as the "dihydrogenphosphate salt... or a hydrate thereof" as that phrase is construed in light of the patent's specification.
V. Key Claim Terms for Construction
The Term: "dihydrogenphosphate salt"
- Context and Importance: This term defines the specific salt claimed by the patent. In pharmaceutical patent litigation, the exact nature of a claimed salt form is often a dispositive issue. Practitioners may focus on this term because Sandoz's non-infringement defense, as outlined in its Paragraph IV certification, could be based on an argument that its API is a different salt or a different polymorphic form of the same salt (Compl. ¶31, ¶51).
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The term itself is a standard chemical name. Parties advocating for a broader scope may argue it should be given its plain and ordinary meaning, covering any composition where the sitagliptin cation and dihydrogenphosphate anion are present in the specified 1:1 molar ratio (’708 Patent, col. 4:46-52).
- Evidence for a Narrower Interpretation: The specification provides extensive detail and characterization data (e.g., X-ray diffraction, NMR) for a specific "crystalline monohydrate" of the salt (’708 Patent, FIG. 1-5). A party could argue that this detailed disclosure implicitly limits the scope of the term to the specific, highly-characterized crystalline forms disclosed in the patent.
The Term: "a hydrate thereof"
- Context and Importance: This phrase provides an alternative to the anhydrous salt form and its scope is critical. The interpretation of this term will determine whether the claim covers only the specific monohydrate detailed in the patent or a wider range of hydrated forms.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The use of the open-ended article "a" could suggest that the claim is not limited to a single type of hydrate (e.g., a monohydrate) but could encompass other stoichiometric hydrates (e.g., dihydrate, hemihydrate) as well.
- Evidence for a Narrower Interpretation: The patent’s abstract, figures, and detailed examples focus almost exclusively on a "crystalline monohydrate" form (’708 Patent, Abstract; col. 4:55-56). A party may argue that the term "a hydrate" should be construed as being limited to the monohydrate form that the inventors actually possessed, described, and characterized in the specification.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Sandoz will actively induce infringement upon approval of its ANDAs. This is based on allegations that Sandoz knows of the patent and that its proposed product labeling will instruct physicians and patients to use the products in an infringing manner (Compl. ¶38-39, ¶58-59).
- Willful Infringement: Willfulness is alleged based on Sandoz having "full knowledge of the '708 patent" from the Paragraph IV notice and proceeding "without a reasonable basis for believing that it would not be liable for infringement" (Compl. ¶43, ¶63).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of structural identity: What is the precise chemical structure, stoichiometry, and crystalline polymorphism of the sitagliptin phosphate API in Sandoz’s proposed generic products, and does that specific form fall within the literal scope of Claim 1?
- A related and dispositive question will be one of claim scope: Can the terms "dihydrogenphosphate salt" and "a hydrate thereof", which are rooted in a specification that heavily details a specific crystalline monohydrate, be construed to cover potentially different polymorphic or amorphous forms that Sandoz may have developed to design around the patent?