DCT

1:22-cv-00615

Gilead Sciences Inc v. Lupin Ltd

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Key Events
Amended Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:22-cv-00615, D. Del., 03/13/2024
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendants are foreign corporations subject to personal jurisdiction in the district. The complaint further alleges that Defendants transact business in Delaware, utilize Delaware-based subsidiaries, and intend to market, distribute, and sell their generic products within the state upon FDA approval.
  • Core Dispute: Plaintiff alleges that Defendants' filing of Abbreviated New Drug Applications (ANDAs) to market generic versions of the HIV-1 treatment drug Biktarvy® constitutes an act of infringement of four U.S. patents covering the drug's active ingredient, its crystalline form, and specific tablet formulations.
  • Technical Context: The technology concerns pharmaceutical compositions for treating Human Immunodeficiency Virus (HIV), a critical area of medicine where combination antiretroviral therapies are the standard of care.
  • Key Procedural History: This action is a Fourth Amended Complaint filed under the Hatch-Waxman Act, triggered by notice letters from each Defendant certifying that the patents-in-suit are invalid or will not be infringed by their proposed generic products. The complaint notes that a previously asserted patent, U.S. Patent No. 9,682,084, has been dismissed from the case.

Case Timeline

Date Event
2014-06-20 Earliest Priority Date for ’342 and ’067 Patents
2015-11-09 Earliest Priority Date for ’846 and ’802 Patents
2017-07-18 ’342 Patent Issued
2018-02-07 Gilead’s Biktarvy® receives initial FDA approval
2019-08-20 ’067 Patent Issued
2020-02-04 ’846 Patent Issued
2022-03-25 Lupin sends first Notice Letter to Gilead
2022-03-30 Laurus sends first Notice Letter to Gilead
2022-03-31 Cipla sends first Notice Letter to Gilead
2023-09-05 ’802 Patent Issued
2023-11-20 Laurus sends second Notice Letter to Gilead (re: ’802 Patent)
2023-11-30 Lupin sends second Notice Letter to Gilead (re: ’802 Patent)
2024-01-29 Cipla sends second Notice Letter to Gilead (re: ’802 Patent)
2024-03-13 Fourth Amended Complaint Filed

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

U.S. Patent No. 9,708,342 - Sodium (2R,5S,13aR)-7,9-dioxo-10-((2,4,6-trifluorobenzyl)carbamoyl)-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazepin-8-olate

The Invention Explained

  • Problem Addressed: The patent background highlights the public health challenge of HIV infection and notes that because standard-of-care treatments require multiple drugs, the potential for drug-drug interactions is a key criterion for selecting a therapeutic regimen (’971 Patent, col. 1:35-50).
  • The Patented Solution: The invention is directed to a specific sodium salt form of an anti-viral compound, known as bictegravir (’971 Patent, col. 2:22-38). This particular salt form (referred to as a compound of Formula II) is claimed to provide a physically stable compound suitable for therapeutic use and manufacturing, addressing the need for reliable antiretroviral therapies (’971 Patent, col. 2:15-19).
  • Technical Importance: Creating a specific, stable salt of an active pharmaceutical ingredient is a critical step in developing a viable drug product with consistent properties.

Key Claims at a Glance

  • The complaint asserts at least claim 1 (Compl. ¶105).
  • Independent Claim 1 consists of a single element:
    • A compound of Formula II, which is the sodium salt of bictegravir.

U.S. Patent No. 10,385,067 - Sodium (2R,5S,13aR)-7,9-dioxo-10-((2,4,6-trifluorobenzyl)carbamoyl)-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazepin-8-olate

The Invention Explained

  • Problem Addressed: The patent addresses the need for effective methods of treating HIV infection using physically stable drug compounds suitable for pharmaceutical formulation (’067 Patent, col. 1:35-50, 2:15-19).
  • The Patented Solution: The patent claims methods of treating HIV by administering a specific crystalline form of the sodium salt of bictegravir (’067 Patent, Abstract). The specification describes this crystalline form, designated "Form I," and characterizes it by specific peaks in an X-ray powder diffraction (XRPD) pattern, which indicates a specific, ordered arrangement of molecules in the solid state (’067 Patent, col. 7:41-51; Fig. 1).
  • Technical Importance: Isolating and claiming a specific crystalline polymorph of a drug ensures batch-to-batch consistency in properties like dissolution rate and bioavailability, which is crucial for safety and efficacy.

Key Claims at a Glance

  • The complaint asserts at least claim 1 (Compl. ¶124).
  • Independent Claim 1 of the ’067 Patent is a method claim with the following essential elements:
    • A method for treating an HIV infection in a human in need thereof,
    • comprising administering to the human a therapeutically effective amount of a compound of Formula II,
    • which is crystalline and is characterized by an x-ray powder diffraction (XRPD) pattern having peaks at about 5.5°, 16.1°, and 23.3° 2-theta±0.2°.

U.S. Patent No. 10,548,846 - Therapeutic compositions for treatment of human immunodeficiency virus

Technology Synopsis

This patent addresses the formulation of a complete HIV treatment regimen into a single tablet. It claims a multi-layer tablet comprising specific amounts of three active ingredients: the compound of Formula I (bictegravir), tenofovir alafenamide, and emtricitabine, with the tablet having a total weight of less than 1000 mg (’846 Patent, Abstract; Compl. ¶47). The multi-layer structure suggests a formulation strategy to manage chemical compatibility or control the release of the different active ingredients.

Asserted Claims

At least claim 1 (Compl. ¶144).

Accused Features

The complaint alleges that Defendants' proposed generic products are multi-layer tablets containing the same three active ingredients in the claimed amounts, falling within the scope of the ’846 patent claims (Compl. ¶145).

U.S. Patent No. 11,744,802 - Therapeutic Compositions for the Treatment of Human Immunodeficiency Virus

Technology Synopsis

This patent is directed to the combination therapy itself in a single dosage form. It claims a tablet (not necessarily multi-layer) comprising 50 mg of bictegravir or its salt, 25 mg of tenofovir alafenamide or its salt, and 200 mg of emtricitabine or its salt (’802 Patent, Abstract; Compl. ¶50). This protects the specific three-drug combination in a tablet form.

Asserted Claims

At least claim 1 (Compl. ¶164).

Accused Features

The complaint alleges that Defendants' proposed products are tablets comprising the same combination of three active ingredients or their salts, thereby infringing the ’802 patent (Compl. ¶165).

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are the proposed generic drug products for which Defendants Lupin Ltd. (ANDA No. 217152), Laurus Labs Limited (ANDA No. 217037), and Cipla Limited (ANDA No. 216914) have filed ANDAs seeking FDA approval (Compl. ¶¶ 51, 68, 85).

Functionality and Market Context

The proposed products are fixed-dose combination tablets intended for the treatment of HIV-1 infection (Compl. ¶¶ 58, 75, 92). The complaint alleges that each Defendant has represented to the FDA that its product contains the same active ingredients (bictegravir, emtricitabine, and tenofovir alafenamide), has the same dosage form and strengths, and is bioequivalent to Gilead’s branded drug, Biktarvy® (Compl. ¶¶ 56, 73, 90). Biktarvy® is described as a complete regimen for HIV-1 treatment and is one of eleven HIV treatments marketed by Gilead (Compl. ¶¶ 4, 36).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

U.S. Patent No. 9,708,342 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A compound of Formula II... The accused ANDA products are alleged to contain bictegravir, which is a compound of Formula II, in a crystalline form, specifically as a sodium salt. ¶41, 107 col. 2:24-38

U.S. Patent No. 10,385,067 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating an HIV infection in a human in need thereof, Defendants' proposed labels for their ANDA products will allegedly instruct for the product's use in treating HIV-1 infection. ¶60, 77, 94, 125 col. 5:1-6
comprising administering... a therapeutically effective amount of a compound of Formula II, The ANDA products contain bictegravir (a compound of Formula II) in a dosage strength bioequivalent to Biktarvy®. ¶56-57, 73-74, 90-91 col. 7:1-12
which is crystalline and is characterized by an x-ray powder diffraction (XRPD) pattern having peaks at about 5.5°, 16.1°, and 23.3° 2-theta±0.2°. The complaint alleges on information and belief that the ANDA products contain a crystalline, polymorphic form of bictegravir. ¶125, 137 col. 7:41-51
  • Identified Points of Contention:
    • Scope Questions: The complaint alleges infringement "either literally or under the doctrine of equivalents" (Compl. ¶107, 125). This suggests a potential dispute over whether the specific crystalline form of bictegravir in the accused products is identical to the "Form I" polymorph characterized in the ’067 Patent, or merely equivalent. The question for the court may be whether the term "crystalline" in the claims is limited to the specific polymorphs disclosed in the specification.
    • Technical Questions: A key evidentiary question will be the physical characterization of the active pharmaceutical ingredient in the Defendants' ANDA products. The complaint alleges on "information and belief" that the products contain a crystalline form of bictegravir (Compl. ¶107, 125). The litigation will require evidence, such as XRPD analysis of the accused products, to determine if they meet the specific claim limitations regarding crystallinity and polymorphic form.

V. Key Claim Terms for Construction

  • The Term: "crystalline"
  • Context and Importance: This term appears in claim 1 of the ’067 Patent and is central to distinguishing the invention from amorphous or other forms of the compound. The infringement analysis for this patent will depend on whether the bictegravir in Defendants' products is "crystalline" as that term is construed. Practitioners may focus on this term because the patent specification provides a detailed characterization of a specific crystalline form ("Form I"), raising the question of whether the claim scope is limited to that form.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The plain meaning of "crystalline" refers generally to a solid material whose constituents are arranged in a highly ordered microscopic structure. Parties advocating for a broader scope may argue that the term should be given its ordinary meaning in chemistry unless the patentee acted as their own lexicographer.
    • Evidence for a Narrower Interpretation: The ’067 patent specification repeatedly and specifically discusses "Form I" of the sodium salt, providing its characteristic XRPD pattern, DSC thermogram, and TGA graph (’067 Patent, Figs. 1-3; col. 7:41-67). The abstract states the invention relates to "Form I." This detailed focus on a single polymorph may support an argument that "crystalline" in the context of this patent should be construed more narrowly to mean the specific Form I disclosed.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced and contributory infringement against all Defendants. The inducement allegations are based on the assertion that Defendants’ proposed product labels will instruct physicians and patients to administer the generic products to treat HIV, thereby encouraging direct infringement of the method claims of the ’067 Patent (Compl. ¶¶ 117, 136).
  • Willful Infringement: The complaint does not contain a formal count for willful infringement. However, it explicitly pleads that each Defendant had "actual knowledge" of the patents-in-suit prior to and at the time of their ANDA submissions, citing the notice letters sent to Gilead (Compl. ¶¶ 66, 83, 100, 113, 132, 152, 171). These allegations of pre-suit knowledge form the basis for a potential future claim for enhanced damages.

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

  • A key evidentiary question will be one of structural identity: Will discovery confirm that the Defendants' generic products contain the specific "Form I" crystalline polymorph of bictegravir sodium as defined and claimed in the ’067 patent, or will the infringement analysis depend on a broader interpretation of "crystalline" or the doctrine of equivalents?
  • A central issue will be one of non-obviousness and claim scope: Given that the asserted patents claim specific salt forms, crystalline structures, and tablet formulations of known active ingredients, the case will likely focus on whether these specific embodiments represent patentably distinct inventions over the prior art, an issue raised by the Defendants' invalidity contentions as described in the complaint.
  • For the formulation patents (’846 and ’802), a critical technical question will be one of functional and structural equivalence: Do the accused generic tablets, particularly the alleged multi-layer structure for the ’846 patent, possess the same structural and functional characteristics as claimed, and are the differences between the formulations, if any, substantial enough to avoid infringement?