DCT

1:23-cv-00508

Gilead Sciences Inc v. Lupin Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-00508, D. Del., 05/09/2023
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware based on the Delaware incorporation of Defendants Lupin Pharmaceuticals, Inc. and MSN Pharmaceuticals Inc., which are alleged to be agents for their foreign parent companies.
  • Core Dispute: Plaintiffs allege that Defendants’ submission of an Abbreviated New Drug Application (ANDA) to the FDA to market a generic version of the HIV treatment SYMTUZA® constitutes an act of infringement of two patents covering the drug's formulation and its specific combination of active ingredients.
  • Technical Context: The dispute involves a fixed-dose combination antiretroviral therapy for HIV, a market where single-tablet regimens are highly valued for improving patient adherence and reducing pill burden.
  • Key Procedural History: The complaint references prior litigation between the parties (Civil Action No. 21-1621, D. Del.) concerning an earlier version of Defendants' ANDA. In that case, Defendants allegedly stipulated to infringing numerous claims of the patents-in-suit. This new action follows Defendants' submission of an amended ANDA and a second notice letter, with Plaintiffs reasserting infringement.

Case Timeline

Date Event
2008-05-02 ’718 Patent Priority Date
2017-07-20 ’518 Patent Priority Date
2018-08-07 ’718 Patent Issue Date
2020-09-29 ’518 Patent Issue Date
2021-10-04 Defendants allegedly send First SYMTUZA Notice Letter
2021-11-16 Plaintiffs commence prior suit against Defendants
2022-11-07 Date of cited stipulation to infringement in prior litigation
2023-04-17 Defendants allegedly submit amended ANDA to FDA
2023-04-17 Defendants allegedly send Second SYMTUZA Notice Letter
2023-05-09 Complaint Filing Date

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 10,039,718 - “Use of Solid Carrier Particles to Improve the Processability of A Pharmaceutical Agent” (Issued Aug. 7, 2018)

The Invention Explained

  • Problem Addressed: The patent describes a specific pharmaceutical agent, the HIV drug cobicistat (referred to as "compound of formula (I)"), as having poor solid-state properties that make it difficult to handle and formulate into tablets on a large scale. These undesirable properties include a low glass transition temperature, hygroscopicity (tendency to absorb moisture), and a non-free-flowing nature. (’718 Patent, col. 2:41-52).
  • The Patented Solution: The invention solves this processability problem by combining the difficult-to-handle cobicistat with "solid carrier particles," specifically hydrophilic fumed silicon dioxide. This combination results in a composition with unexpectedly improved physical properties, including comparatively low hygroscopicity, good flowability, and excellent compressibility, making it suitable for high-volume tablet manufacturing. (’718 Patent, col. 2:11-28). Figure 2 of the patent graphically illustrates this improvement, showing that the combined composition absorbs significantly less water than either cobicistat or the silicon dioxide carrier alone. (’718 Patent, Fig. 2).
  • Technical Importance: This formulation technology enables the efficient manufacturing of a stable, solid oral dosage form for an active pharmaceutical ingredient that would otherwise be challenging to produce commercially. (’718 Patent, col. 2:43-47).

Key Claims at a Glance

  • Asserted Independent Claim: 1
  • Essential Elements of Claim 1:
    • A composition comprising a plurality of hydrophilic fumed silicon dioxide particles
    • and a compound of formula (I) [cobicistat]
    • wherein the compound of formula (I) is in the pores or on the surface of the silicon dioxide particles.
  • The complaint reserves the right to assert additional claims. (Compl. ¶ 78).

U.S. Patent No. 10,786,518 - “Compositions and Methods of Treating HIV” (Issued Sep. 29, 2020)

The Invention Explained

  • Problem Addressed: The patent addresses the problem of "pill burden" in HIV treatment, where patients must take multiple different anti-HIV agents, often in large or frequent doses. This high pill burden can reduce patient adherence to the treatment regimen, which in turn reduces effectiveness and can lead to the emergence of drug-resistant viral strains. (’518 Patent, col. 2:1-9).
  • The Patented Solution: The invention provides a single, once-daily dosage form that combines four specific anti-retroviral agents: darunavir (a protease inhibitor), cobicistat (a pharmacokinetic enhancer), emtricitabine (a nucleoside reverse transcriptase inhibitor), and tenofovir alafenamide (a nucleotide reverse transcriptase inhibitor). This fixed-dose combination simplifies the treatment regimen, thereby reducing pill burden and promoting patient compliance. (’518 Patent, col. 2:10-21).
  • Technical Importance: The development of effective single-tablet regimens represents a significant advance in HIV therapy, directly addressing the critical real-world challenge of long-term patient adherence. (’518 Patent, col. 2:5-9).

Key Claims at a Glance

  • Asserted Independent Claim: 1
  • Essential Elements of Claim 1:
    • A method of treating a subject infected with an HIV virus
    • comprising orally administering to the subject, once daily, a single unit dosage form
    • comprising darunavir (or a hydrate or solvate thereof), cobicistat, emtricitabine, and tenofovir alafenamide (or a pharmaceutically acceptable salt thereof)
    • wherein the subject is treatment experienced and was administered a first anti-retroviral regimen that has been discontinued.
  • The complaint reserves the right to assert additional claims. (Compl. ¶ 113).

III. The Accused Instrumentality

Product Identification

Defendants’ "Reformulated SYMTUZA ANDA Product," identified under ANDA No. 216511. (Compl. ¶¶ 11, 62).

Functionality and Market Context

The accused product is a generic version of Plaintiffs' branded drug SYMTUZA®, intended for the treatment of HIV-1 infection. (Compl. ¶¶ 2, 73). The complaint alleges that by submitting the ANDA, Defendants have represented to the FDA that their product has the same active ingredients, dosage form, and strength as SYMTUZA®, and is bioequivalent to it. (Compl. ¶ 71). A key technical feature alleged in the complaint is that the accused product contains "cobicistat on silicon dioxide ('COBI on SiO2')," which is allegedly manufactured and supplied by Defendant MSN for use in the final product formulated by Defendant Lupin. (Compl. ¶¶ 19, 23).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint alleges that Defendants have previously stipulated in a prior litigation that their ANDA product would infringe numerous claims of the patents-in-suit, including the lead independent claims analyzed below. (Compl. ¶¶ 69, 80, 91, 115). It further alleges that Defendants' notice letters do not contest infringement of most asserted claims. (Compl. ¶¶ 79, 114).

’718 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A composition comprising a plurality of hydrophilic fumed silicon dioxide particles The Reformulated SYMTUZA ANDA Product allegedly contains silicon dioxide as a carrier for the cobicistat active ingredient. ¶19 col. 5:2-7
and a compound of formula (I) The Reformulated SYMTUZA ANDA Product allegedly contains the active ingredient cobicistat. ¶19 col. 2:50-65
wherein the compound of formula (I) is in the pores or on the surface of the silicon dioxide particles. The Reformulated SYMTUZA ANDA Product allegedly contains cobicistat loaded onto silicon dioxide ("COBI on SiO2"). ¶19 col. 5:29-32

’518 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating a subject infected with an HIV virus Defendants' Proposed Label for the ANDA product will allegedly instruct physicians and healthcare providers to administer the product for the treatment of HIV-1 infection. ¶73-74 col. 2:10-14
comprising orally administering to the subject, once daily, a single unit dosage form The ANDA product is allegedly a tablet dosage form intended for once-daily oral administration, consistent with the reference drug SYMTUZA. ¶71 col. 2:14-15
comprising darunavir... cobicistat, emtricitabine, and tenofovir alafenamide... The ANDA product is alleged to contain the same four specified active ingredients as SYMTUZA. ¶71, ¶73 col. 2:15-21
  • Identified Points of Contention: The complaint's repeated references to Defendants' prior stipulations and lack of dispute regarding infringement suggest that the primary legal battle may concern the validity of the patents rather than direct infringement. (Compl. ¶¶ 69, 79, 114). The complaint itself does not articulate specific points of contention over claim scope or technical operation for infringement, instead framing infringement as largely conceded.

V. Key Claim Terms for Construction

  • The Term: "hydrophilic fumed silicon dioxide particles" (’718 Patent, Claim 1)

  • Context and Importance: This term defines the solid carrier, a central component of the '718 patent's formulation. The scope of this term will be critical to infringement. Practitioners may focus on whether this term should be construed to require the specific physical properties (e.g., particle diameter, BET surface area, pore volume) that the patent specification describes as being typical or beneficial for the invention. (Compl. ¶ 19; ’718 Patent, col. 5:2-13).

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The claim language itself does not include any specific numerical limitations on particle size or surface area, which may support a construction covering any fumed silicon dioxide that is hydrophilic.
    • Evidence for a Narrower Interpretation: The detailed description provides specific numerical ranges for these physical properties, stating that "Typically, these silica derivatives comprise a granular hydrophilic fumed silica that has a mean particle diameter of 10 to 120 micron and a BET surface area of 40 to 400 m²/g." (’718 Patent, col. 5:2-7). A defendant could argue these ranges are definitional of the invention.

  • The Term: "single unit dosage form" (’518 Patent, Claim 1)

  • Context and Importance: This term is central to the '518 patent's stated purpose of reducing pill burden. Its definition determines whether the claimed method is practiced. Practitioners may focus on this term because the patent's value is tied to providing a complete HIV regimen in one pill, distinguishing it from multi-pill combinations.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The term itself is generally understood in the pharmaceutical arts to mean a single tablet or capsule. The specification's background emphasizes overcoming the need for "a combination of different anti-HIV agents" taken as multiple pills. (’518 Patent, col. 2:1-4). This may support a broad construction covering any single physical unit containing the four drugs.
    • Evidence for a Narrower Interpretation: The patent provides detailed exemplary formulations for tablets. (’518 Patent, e.g., Table 17). A party seeking a narrower construction might argue that the term should be limited to dosage forms with characteristics similar to those specifically described and enabled in the specification.

VI. Other Allegations

  • Indirect Infringement:
    • ’718 Patent: The complaint alleges inducement and contributory infringement. It claims Defendants will induce infringement through their agreement to manufacture and supply "COBI on SiO2" for the final product. (Compl. ¶ 98-100). It claims contributory infringement on the basis that "COBI on SiO2" is especially made or adapted for this infringing use and is not suitable for substantial non-infringing use. (Compl. ¶ 101).
    • ’518 Patent: The complaint alleges induced infringement based on the Defendants' proposed product label, which will allegedly include instructions for physicians and healthcare providers to administer the product to treat HIV-1, thereby directing them to perform the steps of the claimed method. (Compl. ¶¶ 131, 133-135).
  • Willful Infringement: While the complaint does not use the word "willful," it lays the factual groundwork for such a claim by alleging that Defendants have actual knowledge of the patents. This knowledge is alleged to stem from, among other things, the First and Second SYMTUZA Notice Letters and the prior litigation in which infringement was allegedly stipulated. (Compl. ¶¶ 93-95, 127-129).

VII. Analyst’s Conclusion: Key Questions for the Case

The complaint's emphasis on Defendants' prior stipulations of infringement suggests that the central conflict in this case may revolve around patent validity rather than non-infringement. The key questions for the court will likely be:

  • A core issue will be one of estoppel and waiver: to what extent are Defendants bound by their alleged prior stipulations of infringement from the earlier litigation (Civil Action No. 21-1621), and does the filing of an "amended" ANDA create a new cause of action that allows these infringement questions to be re-litigated?
  • A key question will be one of obviousness: can Defendants prove by clear and convincing evidence that the asserted claims are invalid as obvious? For the '718 patent, this may involve whether combining a known "difficult" API with a standard excipient like fumed silica was a predictable solution. For the '518 patent, it may involve whether combining these four specific, known anti-retroviral drugs into a single tablet was obvious to a person of ordinary skill at the time of the invention.