DCT
2:23-cv-00094
Merck Sharp & Dohme LLC v. Lupin Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Merck Sharp & Dohme LLC (New Jersey)
- Defendant: Lupin Ltd. (India); Lupin Inc. (Delaware); and Lupin Pharmaceuticals, Inc. (Delaware)
- Plaintiff’s Counsel: Gibbons P.C.; Finnegan, Henderson, Farabow, Garrett & Dunner, LLP
- Case Identification: 2:23-cv-00094, D.N.J., 05/19/23
- Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey based on Defendants' systematic and continuous business contacts, including the operation of a manufacturing and research facility in Somerset, New Jersey, and Defendants' prior consent to jurisdiction and venue in the district in other patent cases.
- Core Dispute: Plaintiff alleges that Defendants’ filing of an Abbreviated New Drug Application (ANDA) to market generic versions of Plaintiff's HIV treatment ISENTRESS HD® constitutes an act of infringement of four U.S. patents covering the drug's active ingredient and specific pharmaceutical formulations.
- Technical Context: The technology concerns the HIV integrase inhibitor raltegravir, a key antiretroviral agent, and pharmaceutical compositions designed to improve its stability, solubility, and pharmacokinetic profile for oral administration.
- Key Procedural History: The lawsuit was initiated under the Hatch-Waxman Act following Defendants' submission of ANDA No. 217990 and a corresponding Paragraph IV certification notice letter to Plaintiff, dated November 25, 2022, asserting that the patents-in-suit are invalid, unenforceable, or will not be infringed. This Amended Complaint adds U.S. Patent No. 8,771,733 to the action.
Case Timeline
| Date | Event |
|---|---|
| 2004-12-03 | Priority Date for ’731 and ’733 Patents |
| 2009-10-26 | Priority Date for ’311 and ’888 Patents |
| 2010-07-13 | U.S. Patent No. 7,754,731 Issues |
| 2014-07-08 | U.S. Patent No. 8,771,733 Issues |
| 2017-05-16 | U.S. Patent No. 9,649,311 Issues |
| 2020-09-15 | U.S. Patent No. 10,772,888 Issues |
| 2022-11-25 | Defendants send Paragraph IV Notice Letter to Plaintiff |
| 2023-04-17 | Parties submit Joint Discovery Plan anticipating addition of '733 Patent |
| 2023-05-19 | Amended Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,754,731 - "Potassium Salt of an HIV Integrase Inhibitor"
The Invention Explained
- Problem Addressed: The patent’s background section explains that the free base form of the HIV integrase inhibitor, raltegravir, is not ideal for pharmaceutical use due to poor water solubility, which can negatively impact its pharmacokinetics (Compl., Ex. 1, ’731 Patent, col. 2:1-4). Furthermore, attempts to create a sodium salt resulted in an amorphous, non-crystalline material, which is generally less desirable for formulation due to stability and processing issues (Compl., Ex. 1, ’731 Patent, col. 2:5-7).
- The Patented Solution: The invention provides specific crystalline forms of the potassium salt of raltegravir. The patent describes "Form 1," a specific anhydrous crystalline monopotassium salt, which is disclosed as being significantly more water-soluble than the free base and exhibiting improved pharmacokinetics in animal models (Compl., Ex. 1, ’731 Patent, col. 2:1-4, col. 3:28-34). The crystalline structure is defined by characteristic peaks in an X-ray powder diffraction (XRPD) pattern, illustrated in Figure 1 of the patent (Compl., Ex. 1, ’731 Patent, Fig. 1).
- Technical Importance: For poorly soluble drug compounds, creating a stable, soluble, crystalline salt form is a critical step in developing a viable oral drug product with consistent bioavailability.
Key Claims at a Glance
- The complaint does not specify which claims are asserted, but Claim 1 is the broadest independent claim.
- Essential elements of Independent Claim 1:
- An anhydrous crystalline potassium salt of Compound A (raltegravir).
- The salt is characterized by an X-ray powder diffraction pattern with specific peaks at 2θ values of 5.9, 20.0, and 20.6 degrees.
- The complaint reserves the right to assert additional claims (Compl. ¶48).
U.S. Patent No. 9,649,311 - "Solid Pharmaceutical Compositions Containing an Integrase Inhibitor"
The Invention Explained
- Problem Addressed: The patent suggests a need for a raltegravir-containing tablet that is smaller in weight and volume than the existing Isentress® product and which provides an improved pharmacokinetic profile (Compl., Ex. 2, ’311 Patent, col. 1:49-54).
- The Patented Solution: The patent discloses a compressed tablet formulation with a distinct architecture, comprising an "intragranular component" and an "extragranular component." The intragranular component, formed before the main granulation step, contains the raltegravir salt, a binder, and optionally a first superdisintegrant. The extragranular component, added after granulation, contains a second superdisintegrant, a filler, and a lubricant (Compl., Ex. 2, ’311 Patent, col. 2:27-40). This specific structure is asserted to yield significantly increased drug absorption and reduced variability compared to prior formulations (Compl., Ex. 2, ’311 Patent, col. 3:7-12).
- Technical Importance: The placement of excipients inside or outside the granules in a tablet formulation can significantly affect the tablet's dissolution rate, stability, and ultimately, the drug's absorption in the body.
Key Claims at a Glance
- The complaint does not specify which claims are asserted, but Claim 1 is the broadest independent claim.
- Essential elements of Independent Claim 1:
- A compressed tablet for oral administration.
- Comprising an intragranular component containing: (i) an alkali metal salt of raltegravir, (ii) a first superdisintegrant, and (iii) a binder.
- Comprising an extragranular component containing: (i) a second superdisintegrant, (ii) a filler, and (iii) a lubricant.
- A proviso that the tablet is free of the drug atazanavir.
- The complaint reserves the right to assert additional claims (Compl. ¶54).
U.S. Patent No. 10,772,888 - "Solid Pharmaceutical Compositions Containing an Integrase Inhibitor"
Technology Synopsis
This patent, related to the ’311 patent, also describes compressed tablets of raltegravir with a specific intragranular and extragranular structure. The formulation, which separates key excipients into pre-granulation and post-granulation phases, is designed to achieve an improved pharmacokinetic profile, including higher drug absorption and lower patient-to-patient variability (Compl., Ex. 3, ’888 Patent, col. 3:4-12).
Asserted Claims
The complaint does not specify asserted claims, but the patent includes independent claims 1 and 2.
Accused Features
The overall formulation of Defendants' generic raltegravir tablet is accused of infringing, suggesting it employs the claimed intragranular/extragranular architecture (Compl. ¶60).
U.S. Patent No. 8,771,733 - "Pharmaceutical Composition Containing an Anti-Nucleating Agent"
Technology Synopsis
This patent addresses the problem of a drug salt, such as potassium raltegravir, converting back to its less soluble free form in the acidic environment of the stomach, which would hinder absorption (Compl., Ex. 4, ’733 Patent, col. 1:17-31). The solution is to include an "anti-nucleating agent," such as the polymer HPMC, in the formulation to inhibit or delay this precipitation, thereby maintaining a supersaturated state of the drug and enhancing its potential for absorption (Compl., Ex. 4, ’733 Patent, col. 2:53-59).
Asserted Claims
The complaint does not specify asserted claims, but the patent includes independent claims 1 and 15.
Accused Features
Excipients within Defendants' generic tablet formulation are accused of functioning as the claimed anti-nucleating agent (Compl. ¶66).
III. The Accused Instrumentality
Product Identification
The accused instrumentality is Defendants' generic raltegravir tablet product, for which regulatory approval is sought via ANDA No. 217990 (Compl. ¶1, ¶39).
Functionality and Market Context
The complaint alleges that the accused product is the same as, or substantially the same as, Merck's ISENTRESS HD® 600 mg tablets (Compl. ¶39). As a generic equivalent, the product is intended to provide the same therapeutic effect for the treatment of HIV infection. Upon FDA approval, Defendants intend to engage in the commercial manufacture, use, and sale of the generic product in the United States (Compl. ¶40).
IV. Analysis of Infringement Allegations
The complaint does not provide specific claim charts. The following tables summarize the infringement theory inferred from the allegations that Defendants' ANDA product is a generic version of ISENTRESS HD® and therefore embodies the patented technology.
No probative visual evidence provided in complaint.
’731 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| An anhydrous crystalline potassium salt of Compound A... | The active pharmaceutical ingredient (API) in Defendants' ANDA product is alleged to be the claimed potassium salt. | ¶48 | col. 3:4-7 |
| ...which is characterized by an X-ray powder diffraction pattern obtained using copper Kα radiation which comprises 2θ values in degrees of 5.9, 20.0 and 20.6... | The crystalline structure of Defendants' API is alleged to exhibit the XRPD peaks that define the patented Form 1. | ¶48 | col. 3:11-15; Fig. 1 |
- Identified Points of Contention:
- Evidentiary Question: A central factual dispute will be whether the specific crystalline form of the raltegravir potassium salt used in Defendants' ANDA product exhibits the XRPD pattern required by the asserted claims. The analysis will depend on Defendants' confidential ANDA filing and subsequent characterization data.
’311 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A compressed tablet for oral administration, which comprises: | Defendants' ANDA product is a compressed oral tablet. | ¶54 | col. 4:27-28 |
| (A) an intragranular component comprising: (i) an effective amount of an alkali metal salt of raltegravir, (ii) a first superdisintegrant, and (iii) a binder; and | The formulation of Defendants' tablet is alleged to be manufactured via a process that incorporates the raltegravir API, a superdisintegrant, and a binder pre-granulation. | ¶54 | col. 4:47-52 |
| (B) an extranular component comprising: (i) a second superdisintegrant, (ii) a filler, and (iii) a lubricant... | The formulation of Defendants' tablet is alleged to include the addition of a second superdisintegrant, a filler, and a lubricant to the granules post-granulation. | ¶54 | col. 4:47-52 |
- Identified Points of Contention:
- Technical Question: Does Defendants' manufacturing process for its generic tablet create the distinct "intragranular" and "extragranular" phases as defined in the patent? This will depend on the specific excipients used and the timing of their addition during manufacturing.
- Scope Question: Do the specific excipients used by Defendants (e.g., for binding, filling, and disintegration) fall within the scope of the corresponding claim terms as they would be construed by a court?
V. Key Claim Terms for Construction
- The Term: "intragranular component" and "extragranular component" (’311 Patent)
- Context and Importance: These terms define the core architecture of the claimed formulation. The infringement analysis will depend entirely on whether Defendants' manufacturing process involves adding certain excipients before granulation ("intragranular") and others after ("extranular"). Practitioners may focus on these terms because they tie the claim scope directly to the undisclosed details of Defendants' manufacturing process.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claims themselves do not specify the exact method of granulation (e.g., wet or dry), which could support an argument that the terms apply to a variety of tablet manufacturing processes.
- Evidence for a Narrower Interpretation: The specification explicitly defines the terms based on timing relative to the granulation step: ""intragranular component" refers to the ingredients of the compressed tablet that are incorporated prior to the granulation step, and "extragranular component" refers to the ingredients that are incorporated after granulation" (Compl., Ex. 2, ’311 Patent, col. 4:47-52). This definition may be used to argue for a strict temporal dividing line.
- The Term: "characterized by an X-ray powder diffraction pattern ... which comprises 2θ values in degrees of 5.9, 20.0 and 20.6" (’731 Patent)
- Context and Importance: This phrase defines the patented crystalline structure. The dispute will center on whether Defendants' API meets this structural fingerprint. The term "comprises" suggests the list of peaks is open-ended, but the presence of at least these three is required for literal infringement.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The use of the word "comprises" could support an argument that a crystalline form infringes as long as it contains these three peaks, even if it has additional or shifted peaks.
- Evidence for a Narrower Interpretation: The specification, including Figure 1, provides a detailed XRPD pattern for a specific embodiment (Form 1) (Compl., Ex. 1, ’731 Patent, Fig. 1). Defendants may argue that the claims should be limited to crystalline forms that are substantially identical to this specific disclosed embodiment, considering experimental variability.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that upon approval of the ANDA, Defendants will actively induce and contribute to infringement by marketing and selling the generic product for the treatment of HIV, thereby encouraging and enabling physicians and patients to use the infringing product (Compl. ¶40, ¶49, ¶55, ¶61, ¶67).
- Willful Infringement: The complaint does not use the word "willful," but it lays the groundwork for such a claim by alleging Defendants had actual knowledge of the patents at least as of the date of their Paragraph IV Notice Letter (November 25, 2022) for the '731, '311, and '888 patents, and as of the Joint Discovery Plan (April 17, 2023) for the '733 patent (Compl. ¶47, ¶53, ¶59, ¶65).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of structural and compositional identity: Does the raltegravir API in Defendants’ ANDA product possess the specific crystalline structure defined by the XRPD peaks in the ’731 patent, and does the final tablet formulation embody the specific intragranular/extragranular architecture claimed in the ’311 and ’888 patents? This is a primarily factual question that will be resolved through discovery into Defendants' confidential ANDA.
- A key legal question will be one of functional claim scope: Do the excipients used in Defendants’ formulation perform the function of an "anti-nucleating agent" as that term is understood in the context of the ’733 patent? The answer will depend on the court’s construction of the term and evidence regarding the behavior of Defendants' tablet in a simulated gastric environment.