DCT
2:22-cv-06820
Merck Sharp & Dohme LLC v. Hetero USA Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Merck Sharp & Dohme LLC (New Jersey)
- Defendant: Hetero USA, Inc. (Delaware), Hetero Labs Limited Unit-V (India), and Hetero Labs Limited (India)
- Plaintiff’s Counsel: Saul Ewing LLP
- Case Identification: 2:22-cv-06820, D.N.J., 11/28/2022
- Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey because Defendant Hetero USA maintains a regular and established physical place of business in the district, and the defendants have previously been sued in the district without challenging venue or personal jurisdiction.
- Core Dispute: Plaintiff alleges that Defendants’ submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of the HIV-1 treatment DELSTRIGO® constitutes an act of infringement of two patents covering the drug's bilayer tablet formulation.
- Technical Context: The technology concerns a fixed-dose combination therapy for HIV-1, where three active pharmaceutical ingredients are formulated into a single, stable, bilayer tablet to improve patient adherence and therapeutic efficacy.
- Key Procedural History: The lawsuit was triggered by Defendants’ submission of ANDA No. 217747 with an accompanying Paragraph IV Certification, which alleges that Plaintiff's patents are invalid, unenforceable, and/or will not be infringed by the proposed generic product.
Case Timeline
| Date | Event |
|---|---|
| 2015-12-02 | Earliest Priority Date for '282 and '751 Patents |
| 2018-08-01 | FDA Approval of DELSTRIGO® (month specified) |
| 2020-03-31 | Issue Date of U.S. Patent No. 10,603,282 |
| 2020-11-24 | Issue Date of U.S. Patent No. 10,842,751 |
| 2022-10-15 | Plaintiff received Defendants' Paragraph IV Notice Letter (no earlier than) |
| 2022-11-28 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 10,603,282 - "Pharmaceutical Compositions Containing Doravirine, Tenofovir Disoproxil Fumarate and Lamivudine"
- Patent Identification: U.S. Patent No. 10,603,282, "Pharmaceutical Compositions Containing Doravirine, Tenofovir Disoproxil Fumarate and Lamivudine," issued March 31, 2020.
The Invention Explained
- Problem Addressed: The patent addresses the technical challenge of combining three active drugs for HIV treatment—doravirine, tenofovir disoproxil fumarate (TDF), and lamivudine—into a single, compact tablet ('282 Patent, col. 1:15-26). The specific problems included the physical instability of amorphous doravirine, which tends to crystallize, and the chemical instability of TDF, which is susceptible to hydrolysis, as well as processing issues like poor compactability and dissolution when all three ingredients are simply mixed ('282 Patent, col. 1:50-col. 2:6; col. 4:58-64).
- The Patented Solution: The invention is a bilayer tablet that physically separates the incompatible ingredients. The first layer contains doravirine in an "amorphous dispersion formulation" (mixed with a polymer) to improve its stability and bioavailability. The second layer contains crystalline forms of lamivudine and TDF ('282 Patent, col. 2:54-62). This separation prevents undesirable physical and chemical interactions, allowing for a stable, effective, single-tablet dosage form ('282 Patent, col. 5:3-13).
- Technical Importance: Developing a stable, single-tablet, fixed-dose combination regimen is critical for HIV treatment, as it improves patient compliance and convenience, which are key factors for successful long-term viral suppression ('282 Patent, col. 1:22-26).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 ('Compl. ¶39).
- Essential elements of independent claim 1:
- A pharmaceutical composition, which is a bilayer tablet,
- comprising an amorphous dispersion formulation of doravirine in the first layer, and
- lamivudine and tenofovir disoproxil fumarate in the second layer.
- The complaint does not explicitly reserve the right to assert dependent claims but refers generally to "one or more claims" (Compl. ¶39).
U.S. Patent No. 10,842,751 - "Pharmaceutical Compositions Containing Doravirine, Tenofovir Disoproxil Fumarate and Lamivudine"
- Patent Identification: U.S. Patent No. 10,842,751, "Pharmaceutical Compositions Containing Doravirine, Tenofovir Disoproxil Fumarate and Lamivudine," issued November 24, 2020.
The Invention Explained
- Problem Addressed: As a continuation of the application leading to the '282 Patent, this patent addresses the same technical challenges of formulating a stable, single-tablet, fixed-dose combination of doravirine, TDF, and lamivudine ('751 Patent, col. 1:15-26). These challenges include the physical and chemical incompatibilities of the active ingredients ('751 Patent, col. 5:3-13).
- The Patented Solution: The solution is identical to that described in the '282 Patent: a bilayer tablet structure that physically segregates an amorphous dispersion of doravirine in one layer from the crystalline TDF and lamivudine in a second layer to ensure stability and proper bioperformance ('751 Patent, col. 2:54-62).
- Technical Importance: As described for the '282 Patent, this formulation technology enables a more convenient and reliable treatment regimen for patients with HIV.
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 (Compl. ¶49).
- Essential elements of independent claim 1:
- A tablet comprising a first layer comprising an amorphous dispersion formulation of doravirine, and
- a second layer comprising lamivudine and tenofovir disoproxil fumarate.
- The complaint refers generally to "one or more claims" (Compl. ¶49).
III. The Accused Instrumentality
- Product Identification: The accused product is Defendants' proposed generic version of Merck's DELSTRIGO®, a tablet containing 100 mg of doravirine, 300 mg of lamivudine, and 300 mg of tenofovir disoproxil fumarate (Compl. ¶13). The action is based on Defendants' filing of ANDA No. 217747 seeking FDA approval for this product (Compl. ¶13).
- Functionality and Market Context: The proposed product is intended for the treatment of HIV-1 infection in adult and certain pediatric patients (Compl. ¶10). The complaint alleges that by filing the ANDA, Defendants have represented that their proposed product has the same active ingredients, method of administration, dosage form, strengths, and is bioequivalent to DELSTRIGO® (Compl. ¶17). The filing of the ANDA itself is the statutorily defined act of infringement giving rise to the suit (Compl. ¶37).
- No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint does not include a claim chart. The following tables summarize the infringement theory for claim 1 of each patent, as inferred from the complaint's allegations that the patents-in-suit cover the DELSTRIGO® product (Compl. ¶11) and that Defendants' proposed product is a generic equivalent (Compl. ¶17).
10,603,282 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical composition, which is a bilayer tablet | Defendants' proposed product is alleged to have the same dosage form as DELSTRIGO®, which is a bilayer tablet covered by the patent. | ¶¶11, 13, 17 | col. 2:54-57 |
| comprising an amorphous dispersion formulation of doravirine in the first layer | Defendants' proposed product contains doravirine and is alleged to be bioequivalent to DELSTRIGO®, which uses an amorphous dispersion to achieve necessary bioavailability. | ¶¶13, 17 | col. 2:45-49 |
| and lamivudine and tenofovir disoproxil fumarate in the second layer | Defendants' proposed product contains lamivudine and tenofovir disoproxil fumarate, segregated in a second layer to match the dosage form of DELSTRIGO®. | ¶¶13, 17 | col. 2:59-62 |
10,842,751 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A tablet comprising a first layer comprising an amorphous dispersion formulation of doravirine | Defendants' proposed product is alleged to be a tablet containing a first layer with doravirine formulated as an amorphous dispersion, consistent with the DELSTRIGO® product it copies. | ¶¶11, 13, 17 | col. 2:54-59 |
| and a second layer comprising lamivudine and tenofovir disoproxil fumarate | Defendants' proposed product is alleged to contain a second layer with lamivudine and TDF, consistent with the dosage form of DELSTRIGO®. | ¶¶13, 17 | col. 2:59-62 |
- Identified Points of Contention:
- Structural Questions: The central issue will likely be factual: does the formulation described in Defendants' ANDA specify a "bilayer tablet"? While the complaint alleges this by asserting the proposed product has the same dosage form as DELSTRIGO®, Defendants' Paragraph IV letter asserts non-infringement, suggesting a potential dispute over whether they have designed a different formulation (e.g., a monolithic tablet, a different multi-layer configuration, or co-granulation) that they will argue falls outside the claim scope (Compl. ¶15).
- Scope Questions: What is the precise scope of an "amorphous dispersion formulation of doravirine"? Defendants could argue their method for stabilizing doravirine, if different from the spray-drying method emphasized in the patents' examples, does not meet this limitation as properly construed.
V. Key Claim Terms for Construction
- The Term: "bilayer tablet"
- Context and Importance: This term is the structural foundation of the asserted independent claims in both the '282 and '751 patents. Whether Defendants' proposed product infringes will likely depend entirely on whether it is found to be a "bilayer tablet." Practitioners may focus on this term because a finding of non-infringement could be established if Defendants' formulation is not a two-layer structure, even if it contains the same active ingredients.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claims themselves do not further define the term, which may support an argument for applying its plain and ordinary meaning as understood by a person of ordinary skill in the art of pharmaceutical formulation.
- Evidence for a Narrower Interpretation: The specification consistently and exclusively describes an embodiment with two distinct layers: "An embodiment of the instant invention comprises a bilayer tablet that incorporates high loading of an amorphous dispersion formulation of doravirine in one layer and high loadings of crystalline formulations of lamivudine and tenofovir disoproxil fumarate in a separate layer" ('282 Patent, col. 2:54-62). The detailed examples reinforce this specific two-layer structure, which a defendant may argue limits the term to that configuration.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that upon FDA approval, Defendants will induce infringement by "intentionally encourag[ing] acts of direct infringement" by healthcare professionals and patients (Compl. ¶¶ 40, 50). This encouragement would likely be through the product's labeling and instructions, which would direct the use of the generic product for the patented therapeutic purpose.
- Willful Infringement: The complaint does not use the term "willful," but it lays the groundwork for such a claim and for finding the case exceptional. It alleges that Defendants have had "knowledge of the ['282 and '751] patent[s] since at least the date Hetero submitted Hetero's ANDA" and that their actions "render this an exceptional case under 35 U.S.C. § 285," which is the basis for seeking attorneys' fees (Compl. ¶¶ 42, 52). This alleged knowledge is based on Defendants' statutorily required Paragraph IV Certification against the patents.
VII. Analyst’s Conclusion: Key Questions for the Case
- A primary question for the court will be one of structural identity: Does the formulation detailed in Defendants' confidential ANDA filing describe a "bilayer tablet" that falls within the scope of the asserted claims, or have Defendants engineered an alternative dosage form (e.g., monolithic, multi-particulate) to design around the patents?
- A second key question will be one of invalidity: Assuming Plaintiff demonstrates infringement, the focus will shift to Defendants' affirmative defense, referenced in their Paragraph IV letter, that the asserted patent claims are invalid (Compl. ¶15). The strength of Defendants' prior art or other invalidity theories, which are not detailed in the complaint, will be critical to the ultimate outcome.