DCT

1:22-cv-01399

Gilead Sciences Inc v. Apotex Inc

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:22-cv-01399, D. Del., 10/25/2022
  • Venue Allegations: Plaintiffs allege venue is proper in the District of Delaware because Apotex Corp. is a Delaware corporation and Apotex Inc., a foreign corporation, is subject to personal jurisdiction in the district through systematic business contacts, its filing of an Abbreviated New Drug Application (ANDA) with intent to market products in Delaware, and its previous litigation activity in the district without challenging jurisdiction.
  • Core Dispute: Plaintiffs allege that Defendants' submission of an ANDA to the FDA seeking approval to market a generic version of the HIV treatment drug SYMTUZA® constitutes an act of infringement of five U.S. patents covering pharmaceutical compositions and methods of treating HIV.
  • Technical Context: The patents relate to pharmaceutical formulations and combination therapies for treating Human Immunodeficiency Virus (HIV), a field where single-tablet regimens are critical for improving patient adherence and treatment outcomes.
  • Key Procedural History: This action was filed under the Hatch-Waxman Act, triggered by Apotex’s submission of ANDA No. 217728 and its associated Paragraph IV certification notice letter. The complaint notes a dispute between the parties regarding Plaintiffs' access to the confidential ANDA submission, which Plaintiffs allege has prevented them from fully detailing their infringement contentions.

Case Timeline

Date Event
2008-05-02 U.S. Patent No. 10,039,718 Priority Date
2009-04-03 U.S. Patent Nos. 8,497,396, 9,428,473, and 9,115,100 Priority Date
2013-07-30 U.S. Patent No. 8,497,396 Issues
2015-08-25 U.S. Patent No. 9,115,100 Issues
2016-08-30 U.S. Patent No. 9,428,473 Issues
2018-05-01 U.S. Patent No. 10,786,518 Priority Date
2018-08-07 U.S. Patent No. 10,039,718 Issues
2020-09-29 U.S. Patent No. 10,786,518 Issues
2022-09-12 Apotex sends SYMTUZA Notice Letter to Plaintiffs
2022-10-25 Complaint for Patent Infringement Filed

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"

The Invention Explained

  • Problem Addressed: The patent describes that a specific pharmaceutical compound, cobicistat (referred to as “compound of formula (I)”), has solid-state properties that make it difficult to handle and process on a large scale, including a low glass transition temperature, hygroscopicity (tendency to absorb moisture), and a non-free-flowing nature, which complicates formulation into tablets (’718 Patent, col. 2:45-52).
  • The Patented Solution: The invention combines the difficult-to-process compound with specific solid carrier particles, such as hydrophilic fumed silicon dioxide. This combination results in a free-flowing powder with unexpectedly low hygroscopicity and excellent compressibility, allowing it to be readily processed into stable solid dosage forms like tablets (’718 Patent, col. 2:11-32). Figure 1 of the patent illustrates a manufacturing process flowchart incorporating this solution. (’718 Patent, Fig. 1).
  • Technical Importance: This formulation technology enables the large-scale, commercially viable manufacturing of a specific cytochrome P450 inhibitor (cobicistat) that is used to "boost" the effectiveness of other antiviral drugs (’718 Patent, col. 2:22-26).

Key Claims at a Glance

  • The complaint asserts infringement of claims including independent claim 1 (Compl. ¶¶ 55, 67).
  • Claim 1 requires:
    • A composition comprising a plurality of hydrophilic fumed silicon dioxide particles, and
    • a compound of formula (I) [cobicistat] or a pharmaceutically acceptable salt thereof,
    • wherein the compound of formula (I) is in the pores or on the surface of the silicon dioxide particles.
  • The complaint also asserts claims 5 and 14, which depend from claim 1 (Compl. ¶67).

U.S. Patent No. 10,786,518 - "Compositions and Methods of Treating HIV"

The Invention Explained

  • Problem Addressed: The patent addresses the need for effective HIV inhibitory therapy that reduces "pill burden," which is the large number and/or volume of dosage forms that patients must take, often on a frequent basis. High pill burden can lead to non-adherence, reduced treatment effectiveness, and the emergence of viral resistance (’518 Patent, col. 2:5-9, col. 1:60-65).
  • The Patented Solution: The patent discloses a single-unit, once-daily dosage form that combines four specific anti-HIV agents: darunavir (a protease inhibitor), cobicistat (a pharmacokinetic enhancer), emtricitabine (a nucleoside reverse transcriptase inhibitor), and tenofovir alafenamide (a nucleotide reverse transcriptase inhibitor). This single-tablet regimen is designed to provide a complete and effective HIV treatment, thereby improving convenience and patient compliance (’518 Patent, col. 2:10-21, Abstract).
  • Technical Importance: The invention provides a complete, fixed-dose combination therapy in a single tablet, which is a significant advancement in managing HIV by simplifying treatment regimens for patients.

Key Claims at a Glance

  • The complaint asserts infringement of claims including independent claim 1 (Compl. ¶¶ 94, 103).
  • Claim 1 requires:
    • A method of treating a subject infected with HIV-1,
    • comprising orally administering to the subject, once daily, a single unit dosage form comprising darunavir, 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, and
    • wherein the subject exhibits a viral load of less than or equal to 50 copies/mL of blood plasma, after at least 24 weeks of the once-daily administration.
  • The complaint generally alleges infringement of "at least one of the claims" of the patent (Compl. ¶94).

Multi-Patent Capsule: U.S. Patent No. 8,497,396

  • Patent Identification: U.S. Patent No. 8,497,396, "Methods and Intermediates for Preparing Pharmaceutical Agents," issued July 30, 2013 (Compl. ¶31).
  • Technology Synopsis: The patent discloses improved synthetic methods and novel chemical intermediates for preparing cobicistat, a cytochrome P450 monooxygenase inhibitor. The described synthetic route is intended to reduce the cost, time, and waste associated with manufacturing the compound (’396 Patent, col. 1:46-55).
  • Asserted Claims: Independent claims 1 and 2 are asserted (Compl. ¶126).
  • Accused Features: The Apotex ANDA product is alleged to include cobicistat as a component, which Plaintiffs allege on information and belief is manufactured using a process claimed in the patent (Compl. ¶¶ 126-128).

Multi-Patent Capsule: U.S. Patent No. 9,428,473

  • Patent Identification: U.S. Patent No. 9,428,473, "Methods and Intermediates for Preparing Pharmaceutical Agents," issued August 30, 2016 (Compl. ¶32).
  • Technology Synopsis: This patent, related to the ’396 patent, also discloses improved synthetic methods and novel chemical intermediates for the preparation of cobicistat. The methods are designed to be more efficient for large-scale production (’473 Patent, col. 1:47-55).
  • Asserted Claims: Independent claims 1, 9, and 16 are asserted (Compl. ¶149).
  • Accused Features: The Apotex product's inclusion of cobicistat, which is alleged to be made by a process claimed in the patent (Compl. ¶¶ 149-151).

Multi-Patent Capsule: U.S. Patent No. 9,115,100

  • Patent Identification: U.S. Patent No. 9,115,100, "Methods and Intermediates for Preparing Pharmaceutical Agents," issued August 25, 2015 (Compl. ¶33).
  • Technology Synopsis: This patent, also in the same family as the ’396 and ’473 patents, discloses additional synthetic methods and intermediates for preparing cobicistat. The invention provides an alternative synthetic route for manufacturing the pharmaceutical agent (’100 Patent, col. 1:49-56).
  • Asserted Claims: Claims 1 to 4 are asserted (Compl. ¶172).
  • Accused Features: The Apotex product's inclusion of cobicistat, which is alleged to be made by a process claimed in the patent (Compl. ¶¶ 172-174).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality is the "Apotex SYMTUZA ANDA Product," a generic drug for which Apotex seeks FDA approval via ANDA No. 217728 (Compl. ¶¶ 12, 38).
  • Functionality and Market Context: The complaint alleges that the Apotex product is a generic copy of Janssen’s SYMTUZA®, a "highly successful product" for the treatment of HIV-1 infection (Compl. ¶2, ¶34). It is alleged to contain the same four active ingredients—darunavir, cobicistat, emtricitabine, and tenofovir alafenamide—in the same dosage forms and strengths as SYMTUZA®, and to be bioequivalent (Compl. ¶43). Apotex is seeking approval to manufacture, import, market, and sell this product in the United States prior to the expiration of the patents-in-suit (Compl. ¶12). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

U.S. Patent No. 10,039,718 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... On information and belief, the Apotex SYMTUZA ANDA Product will include cobicistat on silicon dioxide (SiO2) as a component. ¶69 col. 5:3-12
and a compound of formula (I) or a pharmaceutically acceptable salt thereof... The Apotex product is alleged to contain cobicistat, which is the compound of formula (I). ¶44 col. 2:6-8
wherein the compound of formula (I) is in the pores or on the surface of the silicon dioxide particles. The complaint alleges the Apotex product will include "COBI on SiO2 as a component," which implies the compound is on the surface of or within the pores of the carrier. ¶69 col. 5:29-32

U.S. Patent No. 10,786,518 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating a subject infected with HIV-1, comprising orally administering to the subject, once daily, a single unit dosage form comprising darunavir, cobicistat, emtricitabine, and tenofovir alafenamide... On information and belief, Apotex's proposed label will instruct physicians and healthcare providers to administer the Apotex product, a four-drug combination, for the treatment of HIV-1 infection. ¶¶ 44, 45, 108 col. 2:10-21
wherein the subject is treatment experienced and was administered a first anti-retroviral regimen that has been discontinued... The proposed label will allegedly contain data relating to the treatment of patients with HIV-1 infection obtained from clinical studies involving SYMTUZA®, which was studied in such patient populations. ¶46 col. 2:21-24

Identified Points of Contention

  • Evidentiary Questions: The complaint is based on "information and belief" due to Plaintiffs' alleged lack of access to the confidential ANDA filing (Compl. ¶¶ 49, 52). A central point of contention will be an evidentiary one: what does discovery of the ANDA and its supporting Drug Master Files (DMFs) reveal about the actual composition and manufacturing process of the Apotex product?
  • Scope Questions (’718 Patent): Does the silicon dioxide carrier allegedly used by Apotex meet the claim limitation of "hydrophilic fumed silicon dioxide particles"? The analysis will depend on the specific characteristics of Apotex’s chosen excipient.
  • Technical Questions (’518 Patent): Will the final, FDA-approved label for the Apotex product instruct administration to a patient population that meets all limitations of the method claim, including that the subject is "treatment experienced" and meets specific viral load criteria as claimed?

V. Key Claim Terms for Construction

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

  • Context and Importance: This term is the central technical limitation of the asserted composition claim. The infringement analysis for the ’718 patent will hinge on whether the carrier used in the Apotex product falls within the scope of this term, as opposed to other forms of silicon dioxide or other excipients.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent specification refers more generally to "silica derivatives" and "fumed silica" as suitable solid carriers, suggesting the specific type may not be narrowly limited (’718 Patent, col. 2:14, col. 5:15-16).
    • Evidence for a Narrower Interpretation: The specification provides a detailed description of a specific preferred embodiment, AEROPERL® 300, and lists its particular properties, such as a mean grain diameter of 20-40 microns and a specific BET surface area, which could be argued to define the scope of the claimed particles (’718 Patent, col. 5:14-30).

Term: "treatment experienced" (’518 Patent, Claim 1)

  • Context and Importance: This term defines the patient population covered by the asserted method claim. The scope of this term is critical for determining whether the intended use described on Apotex's proposed label will induce infringement.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent defines the term broadly as a subject who "was administered a first anti-retroviral regimen that has been discontinued" (’518 Patent, col. 2:21-24).
    • Evidence for a Narrower Interpretation: The detailed description and clinical trial data incorporated into the patent focus on patients who were virologically suppressed on a prior regimen before switching (’518 Patent, Abstract, Example 1). A defendant may argue that the term should be limited to this specific clinical context, rather than any patient who has ever previously taken an antiretroviral.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement for the composition and process patents, and induced infringement for the method patent. For the ’518 method patent, inducement is alleged based on Apotex's proposed label, which will allegedly instruct physicians and patients to administer the drug in an infringing manner (Compl. ¶¶ 108-112). For the other patents, inducement is alleged based on Apotex's intent to "actively induce, encourage, aid and abet the commercial manufacture, use, offer for sale, and/or sale" of the infringing product (Compl. ¶75, ¶133). Contributory infringement is alleged on the basis that Apotex knows its components are "especially made or adapted for use in infringing" the patents and are "not suitable for substantial non-infringing use" (Compl. ¶77, ¶135).
  • Willful Infringement: The complaint does not contain a separate count for willful infringement. However, it repeatedly alleges that Apotex has had "actual knowledge" of each patent-in-suit "no later than the filing of its Apotex SYMTUZA ANDA," which could form the basis for a later willfulness claim (Compl. ¶¶ 57, 72, 92, 104, 130, 153, 176).

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

  • A primary issue will be one of evidentiary proof: As Plaintiffs have filed this complaint without access to the confidential ANDA, the case will initially turn on what discovery reveals about the actual composition of the Apotex product. Specifically, does it contain cobicistat formulated on "hydrophilic fumed silicon dioxide particles" as claimed in the ’718 patent, and was it manufactured using the processes of the ’396, ’473, and ’100 patents?
  • A second core issue will be one of induced infringement: Does the language of Apotex's proposed label, which will eventually be produced in discovery, actively encourage and instruct physicians to administer the generic drug to the specific "treatment experienced" patient population defined in claim 1 of the ’518 patent?
  • A key legal and technical question will be one of claim scope: How broadly will the court construe the term "hydrophilic fumed silicon dioxide particles" in the ’718 patent? The case may turn on whether the term is limited to the specific commercial examples with defined physical properties disclosed in the patent, or if it covers a wider range of silica-based excipients.