DCT
1:19-cv-01489
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: Williams & Connolly LLP
- Case Identification: 1:19-cv-00101, N.D. W. Va., 05/02/2019
- Venue Allegations: Venue is alleged to be proper in the Northern District of West Virginia because Defendant Mylan Pharmaceuticals Inc. is a West Virginia corporation, and Defendant Mylan Inc. has allegedly consented to venue in the district.
- Core Dispute: Plaintiff alleges that Defendants' submission of Abbreviated New Drug Applications (ANDAs) to the FDA seeking to market generic versions of the diabetes drugs JANUVIA® and JANUMET® constitutes an act of patent infringement.
- Technical Context: The technology concerns pharmaceutical compounds and formulations for treating Type 2 diabetes, specifically involving a dipeptidyl peptidase-IV (DPP-4) inhibitor.
- Key Procedural History: The complaint alleges that Defendants provided notice of their ANDA filings via letters dated December 28, 2010, and September 13, 2013, indicating pre-suit knowledge of the patents. The provided patent documents for U.S. Patent No. 7,326,708 include an Inter Partes Review (IPR) Certificate, indicating that several claims, including asserted independent claim 1, survived a patentability challenge at the U.S. Patent and Trademark Office.
Case Timeline
| Date | Event |
|---|---|
| 2003-06-24 | U.S. Patent No. 7,326,708 Priority Date |
| 2005-12-16 | U.S. Patent No. 8,414,921 Priority Date |
| 2008-02-05 | U.S. Patent No. 7,326,708 Issued |
| 2010-12-28 | Mylan sends notice letter for ANDAs against the ’708 Patent |
| 2013-04-09 | U.S. Patent No. 8,414,921 Issued |
| 2013-09-13 | Mylan sends notice letter for ANDA amendment against the ’921 Patent |
| 2019-05-02 | 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 identifies inhibition of dipeptidyl peptidase-IV (DP-IV) as a novel approach to treating Type 2 diabetes (Compl. ¶28; ’708 Patent, col. 1:31-44). While a prior patent application disclosed the base chemical compound, this patent addresses the subsequent challenge of creating a form of that compound with properties suitable for pharmaceutical manufacturing, such as improved physical and chemical stability (’708 Patent, col. 2:5-16).
- The Patented Solution: The invention is a specific salt form of the active pharmaceutical ingredient: 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 (’708 Patent, Abstract). This salt form, particularly as a crystalline monohydrate, is described as having advantages in processing and handling, and exhibiting improved stability and solubility, making it "particularly suitable for the manufacture of various pharmaceutical dosage forms" (’708 Patent, col. 2:5-19).
- Technical Importance: The development of a stable, manufacturable salt form is a critical step in translating a promising chemical compound into a viable, mass-produced drug product for treating a widespread condition like Type 2 diabetes (’708 Patent, col. 2:10-19).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 (Compl. ¶43).
- 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 reserves the right to assert additional claims (Compl. ¶31).
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 section 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 (’921 Patent, col. 1:19-29). The technical challenge is to combine two different active ingredients, such as a DPP-4 inhibitor and metformin, into a single, stable, and effective fixed-dose tablet (’921 Patent, col. 1:29-41).
- The Patented Solution: The invention provides a specific pharmaceutical formulation that combines sitagliptin (a DPP-4 inhibitor) and metformin into a single tablet. The patent claims a composition defined by specific weight percentage ranges of the two active ingredients along with ranges for key excipients, including a lubricant, a binding agent, a surfactant, and a diluent, to create a viable immediate-release dosage form (’921 Patent, Abstract; col. 12:49-61).
- Technical Importance: This fixed-dose combination tablet simplifies treatment for Type 2 diabetes patients by delivering two drugs with complementary mechanisms of action in a single dosage form, which may improve patient adherence to therapy (’921 Patent, col. 1:29-34).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 (Compl. ¶82).
- The essential elements of independent claim 1 are 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 reserves the right to assert additional claims (Compl. ¶38).
III. The Accused Instrumentality
Product Identification
The accused instrumentalities are Defendants' generic drug products as described in Abbreviated New Drug Application (ANDA) No. 202473 ("Mylan's '473 ANDA Product") and ANDA No. 202478 ("Mylan's '478 ANDA Product") (Compl. ¶1).
Functionality and Market Context
- The '473 ANDA Product is a generic version of Merck’s JANUVIA® and is alleged to contain "sitagliptin phosphate as an active ingredient" (Compl. ¶¶3, 42).
- The '478 ANDA Product is a generic version of Merck’s JANUMET® and is alleged to be a combination product containing "generic metformin hydrochloride and sitagliptin phosphate" (Compl. ¶¶4, 6).
- The complaint alleges that by filing these ANDAs, Defendants seek FDA approval to manufacture and sell these generic products in the U.S. market before the expiration of the patents-in-suit. Under the Hatch-Waxman Act, the submission of such an ANDA is a statutory act of infringement (Compl. ¶¶1, 45, 83).
IV. Analysis of Infringement 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... or a hydrate thereof. | Mylan’s '473 and '478 ANDA Products are alleged to contain "sitagliptin phosphate as an active ingredient." | ¶42, ¶43, ¶62, ¶63 | col. 2:45-52 |
- Identified Points of Contention: The complaint alleges that in its notice letters, "Mylan did not contest infringement of claim 1 of the '708 patent" (Compl. ¶¶44, 64). However, the complaint also states that Mylan filed a certification with the FDA asserting that the ’708 Patent is "invalid, unenforceable, and/or will not be infringed" (Compl. ¶¶41, 61). This suggests the primary dispute regarding the ’708 Patent may center on questions of validity and enforceability rather than claim scope or technical operation.
’921 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| (a) about 3 to 20% by weight of sitagliptin... | The composition of Mylan's '478 ANDA Product includes the same or equivalent ingredients... in the same or equivalent amounts. | ¶82 | col. 12:51-53 |
| (b) about 25 to 94% by weight of metformin hydrochloride; | The composition of Mylan's '478 ANDA Product includes the same or equivalent ingredients... in the same or equivalent amounts. | ¶82 | col. 12:54-55 |
| (c) about 0.1 to 10% by weight of a lubricant; | The composition of Mylan's '478 ANDA Product includes the same or equivalent ingredients... in the same or equivalent amounts. | ¶82 | col. 12:56-57 |
| (d) about 0 to 35% by weight of a binding agent; | The composition of Mylan's '478 ANDA Product includes the same or equivalent ingredients... in the same or equivalent amounts. | ¶82 | col. 12:58-59 |
| (e) about 0.5 to 1% by weight of a surfactant; and | The composition of Mylan's '478 ANDA Product includes the same or equivalent ingredients... in the same or equivalent amounts. | ¶82 | col. 12:60 |
| (f) about 5 to 15% by weight of a diluent. | The composition of Mylan's '478 ANDA Product includes the same or equivalent ingredients... in the same or equivalent amounts. | ¶82 | col. 12:61 |
- Identified Points of Contention: The complaint’s allegation of infringement for the ’921 Patent is conclusory, stating the accused product contains the "same or equivalent ingredients" in the "same or equivalent amounts" (Compl. ¶82). A central technical question will be whether the specific formulation defined in Mylan’s '478 ANDA meets all six of the claimed weight-percentage ranges. This raises a potential claim construction issue regarding the scope of the term "about," as discussed in Section V.
No probative visual evidence provided in complaint.
V. Key Claim Terms for Construction
The complaint does not provide sufficient detail for analysis of key claim terms for the ’708 Patent. For the ’921 Patent:
- The Term: "about"
- Context and Importance: This term modifies every numerical range in asserted claim 1 of the ’921 Patent. The determination of infringement will depend on whether the weight percentages of the components in Mylan's accused product fall within the claimed ranges. The interpretation of "about" could be dispositive, as a narrow reading may place the accused product outside the claim scope, while a broader reading may place it inside. Practitioners may focus on this term because its inherent flexibility makes its precise meaning a common subject of dispute in chemical and formulation patents.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent uses the term "about" extensively in the specification when describing dosage strengths and formulation examples, such as "an amount from about 1 milligram to about 250 milligrams" of the active moiety (’921 Patent, col. 4:6-8). This consistent use in a non-limiting context could suggest the patentee intended the term to afford a degree of flexibility beyond literal numerical identity.
- Evidence for a Narrower Interpretation: The claims recite specific and relatively narrow ranges, such as "about 0.5 to 1% by weight of a surfactant" (’921 Patent, col. 12:60). A court may find that such specificity, even when preceded by "about," signals an intent to limit the scope to only minor variations that account for standard experimental or manufacturing tolerances, rather than a substantial expansion of the claimed ranges.
VI. Other Allegations
- Indirect Infringement: The complaint alleges both induced and contributory infringement for both patents. The inducement allegations are based on Defendants' alleged knowledge of the patents and intent to cause infringement through proposed product labeling that will instruct medical professionals and patients on an infringing use (Compl. ¶¶48-49, 86-87). The contributory infringement allegations are based on the assertion that the ANDA products are not staple articles of commerce and are especially made or adapted for an infringing use (Compl. ¶¶50, 88).
- Willful Infringement: The complaint alleges that Defendants acted with "full knowledge" of the patents-in-suit and "without a reasonable basis for believing" they would not be liable for infringement (Compl. ¶¶53, 91). This claim is predicated on Defendants' alleged pre-suit knowledge, evidenced by the notice letters sent to Merck in 2010 and 2013 (Compl. ¶¶2, 5).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue for the ’708 Patent appears to be patent validity. While the complaint alleges that infringement was not contested by Mylan, it also notes that Mylan filed a Paragraph IV certification with the FDA asserting the patent is invalid and/or unenforceable. The patent’s survival of a subsequent IPR proceeding, as noted on the patent certificate, will likely be a significant factor in the litigation of this issue.
- A key evidentiary question for the ’921 Patent will be one of compositional identity. The case may turn on whether discovery reveals that the formulation in Mylan’s '478 ANDA meets every specific weight-percentage limitation recited in Claim 1.
- A critical legal question impacting the '921 Patent analysis will be one of definitional scope: how broadly will the court construe the term "about"? The resolution of this claim construction issue may determine whether Mylan's specific formulation falls within the scope of the asserted claims.