DCT
1:19-cv-00315
Merck Sharp & Dohme Corp v. Mylan Pharma Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Merck Sharp & Dohme Corp. (New Jersey)
- Defendant: Mylan Pharmaceuticals Inc. (West Virginia) and Mylan Inc. (Pennsylvania)
- Plaintiff’s Counsel: McCarter & English, LLP; Williams & Connolly LLP
- Case Identification: 1:19-cv-00315, D. Del., 02/13/2019
- Venue Allegations: Plaintiff alleges venue is proper in Delaware because Defendants have purposefully availed themselves of the state's laws, transact business there, derive substantial revenue from products used in the state, and will market the accused generic products in Delaware upon approval.
- Core Dispute: Plaintiff alleges that Defendant’s submission of Abbreviated New Drug Applications (ANDAs) to the FDA for generic versions of the diabetes drugs JANUVIA® and JANUMET® constitutes an act of infringement of two patents covering the drug's active ingredient salt form and its combination with metformin.
- Technical Context: The technology relates to pharmaceutical compositions for treating Type 2 diabetes, a condition with a large and established pharmaceutical market.
- Key Procedural History: This action arises under the Hatch-Waxman Act, triggered by notice letters sent by Mylan to Merck. The letters announced Mylan's filing of two ANDAs with Paragraph IV certifications, asserting that Merck's patents are invalid, unenforceable, or will not be infringed by Mylan's proposed generic products. The complaint notes that for the '708 patent, Mylan did not contest infringement of at least Claim 1 in its notice letters.
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 |
| 2010-12-28 | Mylan's '473 ANDA and First '478 ANDA Notice Letters Sent |
| 2013-04-09 | U.S. Patent 8,414,921 Issue Date |
| 2013-09-13 | Mylan's Second '478 ANDA Notice Letter Sent |
| 2019-02-13 | 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: While the active pharmaceutical ingredient sitagliptin was previously known, the patent addresses the need for a form of the compound with advantageous properties for manufacturing pharmaceutical compositions, such as improved physical and chemical stability and better physicochemical properties like solubility ('708 Patent, col. 2:5-16).
- The Patented Solution: The patent discloses a specific salt of sitagliptin—the dihydrogenphosphate salt. The specification places particular emphasis on a crystalline monohydrate form of this salt, which is described as having improved stability to heat and humidity, making it "particularly suitable for the manufacture of various pharmaceutical dosage forms" ('708 Patent, Abstract; col. 2:10-16). The patent provides detailed characterization data for this crystalline form, including its X-ray diffraction pattern (FIG. 1), which serves as a fingerprint for its physical structure ('708 Patent, col. 2:26-29).
- Technical Importance: Developing a stable, crystalline salt form of a drug is a critical step in pharmaceutical development, as it allows for consistent, large-scale manufacturing and ensures the drug product has a predictable shelf life and reliable bioavailability for patients ('708 Patent, col. 2:5-16).
Key Claims at a Glance
- The complaint asserts infringement of "one or more claims... including at least claim 1" (Compl. ¶¶40, 60).
- Independent Claim 1 recites:
- 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's background notes that long-term treatment of Type 2 diabetes often requires combination therapy. However, prescribing multiple, separate medications can lead to complex regimens that are difficult for patients to follow, potentially reducing compliance ('921 Patent, col. 1:21-29).
- The Patented Solution: The invention provides a fixed-dose combination tablet that includes both a DPP-4 inhibitor (such as sitagliptin) and metformin. The claims define a specific formulation, reciting ranges of weight percentages for the two active ingredients as well as for several inactive ingredients (excipients) like lubricants, binders, surfactants, and diluents ('921 Patent, Abstract; col. 4:55-65). This specific recipe is intended to create a stable and effective immediate-release tablet.
- Technical Importance: Fixed-dose combination tablets can simplify treatment for patients with chronic diseases, improving adherence to the prescribed therapy and, consequently, improving health outcomes ('921 Patent, col. 1:29-32).
Key Claims at a Glance
- The complaint asserts infringement of "one or more claims... including at least claim 1" (Compl. ¶79).
- Independent Claim 1 recites 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 instrumentalities are Mylan’s proposed generic drug products identified in ANDA No. 202473 and ANDA No. 202478 (Compl. ¶1).
Functionality and Market Context
- The product specified in ANDA No. 202473 is a generic version of Merck’s JANUVIA® and contains sitagliptin phosphate as its active ingredient (Compl. ¶¶3, 39).
- The product specified in ANDA No. 202478 is a generic version of Merck’s JANUMET® and is alleged to contain sitagliptin phosphate and metformin hydrochloride (Compl. ¶¶6, 59; '921 Patent, Claim 1).
- The complaint alleges that these ANDA submissions, which seek FDA approval to market the generic drugs before the expiration of the patents-in-suit, constitute a statutory act of infringement under 35 U.S.C. § 271(e)(2) (Compl. ¶¶42, 62, 80).
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
’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... or a hydrate thereof. | The accused ANDA products ('473 and '478) are alleged to contain "sitagliptin phosphate as an active ingredient," which is the dihydrogenphosphate salt covered by the claim. | ¶¶39, 40, 59, 60 | col. 2:1-4 |
’921 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| 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. | The complaint alleges that the composition of Mylan's '478 ANDA Product "includes the same or equivalent ingredients as recited in claim 1 of the '921 patent in the same or equivalent amounts." | ¶79 | col. 12:48-59 |
- Identified Points of Contention:
- Scope Questions: For the ’708 Patent, a potential question is whether the "sitagliptin phosphate" in Mylan's product is the specific "dihydrogenphosphate salt" recited in Claim 1. The complaint alleges Mylan did not contest infringement of this claim, which suggests the primary dispute may concern validity (Compl. ¶¶41, 61). However, infringement of dependent claims covering the specific crystalline monohydrate form could remain a point of technical dispute, centering on the polymorphic form of Mylan's active ingredient.
- Technical Questions: For the ’921 Patent, the infringement allegation is stated in a conclusory manner (Compl. ¶79). A central technical question will be whether Mylan's proposed generic formulation, as detailed in its confidential ANDA submission, actually meets the specific weight percentage ranges for all six recited components. This will be a fact-intensive inquiry dependent on evidence produced during discovery.
V. Key Claim Terms for Construction
For the ’708 Patent:
- The Term: "a dihydrogenphosphate salt"
- Context and Importance: This term defines the chemical composition of the invention. While the complaint alleges Mylan does not contest infringement, the scope of this term could be relevant to the analysis of dependent claims and validity. Practitioners may focus on this term because the patent specification heavily emphasizes the discovery of a specific "crystalline monohydrate" as a key inventive aspect ('708 Patent, Abstract).
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: Claim 1 itself recites "a dihydrogenphosphate salt... or a hydrate thereof," without expressly limiting the salt to a particular crystalline or polymorphic form, which could support a construction covering any such salt of sitagliptin ('708 Patent, col. 14:62-67).
- Evidence for a Narrower Interpretation: The specification repeatedly highlights the advantages of a "crystalline monohydrate" of the dihydrogenphosphate salt ('708 Patent, col. 2:4-5), and provides extensive data (X-ray, NMR, DSC) specific to that form (FIGS. 1-5). A party could argue that the claims, read in light of this disclosure, should be construed as being tied to the properties of this specific, stable crystalline form.
For the ’921 Patent:
- The Term: "about"
- Context and Importance: This term precedes every weight percentage range in Claim 1. Its interpretation is critical because it determines the literal boundaries of the claimed formulation. Infringement will depend on whether the precise percentages in Mylan's product fall within the claimed ranges, as modified by the scope of "about."
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The term is not explicitly defined, suggesting it should be given its ordinary meaning in the context of pharmaceutical formulation, which generally implies some level of tolerance for minor variations in measurements and manufacturing ('921 Patent, col. 12:48-59).
- Evidence for a Narrower Interpretation: A party could argue that in the context of an FDA-regulated pharmaceutical composition, the ranges should be interpreted with less flexibility. The patent does not provide an explicit definition or range for "about," leaving its precise scope as a question for the court.
VI. Other Allegations
- Indirect Infringement: The complaint alleges active inducement, stating that Mylan's proposed product labeling will instruct physicians and patients to use the generic products in an infringing manner and that Mylan has knowledge of the patents via its notice letters (Compl. ¶¶46, 66, 84). It also alleges contributory infringement, asserting that Mylan's products are not staple articles of commerce and are especially adapted for infringing use (Compl. ¶¶47, 67, 85).
- Willful Infringement: Willfulness is alleged based on Mylan's pre-suit knowledge of the patents, as evidenced by its notice letters and Paragraph IV certifications, and its intent to market the products "without a reasonable basis for believing that it would not be liable for infringement" (Compl. ¶¶50, 70, 88).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of validity: As this is a Hatch-Waxman case initiated after Mylan's Paragraph IV certification, and given the complaint's allegation that infringement of the '708 patent was not contested by Mylan, the core of the dispute will likely focus on Mylan's defenses that the patents are invalid or unenforceable.
- A key evidentiary question will be one of compositional identity: For the '921 patent, does the precise formulation disclosed in Mylan's '478 ANDA fall within the specific weight-percentage ranges of Claim 1? The resolution will depend on facts revealed in discovery concerning Mylan's composition and the court's construction of the term "about."
- A secondary question for the '708 patent may be one of polymorphic form: While infringement of Claim 1 appears to be less contentious, should the case proceed on dependent claims, a key technical question will be whether Mylan's ANDA specifies the use of the particular "crystalline monohydrate" form of sitagliptin phosphate that is a focus of the patent's disclosure.