DCT

3:19-cv-00529

Gilead Sciences Inc v. Zydus Pharma USA Inc

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:

  • Case Identification: 3:19-cv-00529, D.N.J., 01/15/2019

  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Zydus Pharmaceuticals (USA) Inc. is incorporated in New Jersey.

  • Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) to market a generic version of the HIV treatment Truvada® constitutes an act of infringement of six patents related to the drug's active ingredients and stable pharmaceutical formulations.

  • Technical Context: The technology concerns antiretroviral therapies for treating Human Immunodeficiency Virus (HIV), a market with significant public health and commercial importance.

  • Key Procedural History: This is a Hatch-Waxman action filed under 35 U.S.C. § 271(e)(2), triggered by a Paragraph IV certification notice letter dated December 3, 2018, in which Defendants challenged the validity and/or infringement of the patents-in-suit in connection with ANDA No. 212689. The complaint was filed within the statutory 45-day window, triggering an automatic 30-month stay of FDA approval for the ANDA. The complaint also notes a typographical error in Claim 1 of U.S. Patent No. 8,716,264, stating that Plaintiff will request a court correction.

Case Timeline

Date Event
1990-02-01 Priority Date for ’245 and ’396 Patents
2003-01-14 Priority Date for ’397, ’264, ’036, and ’181 Patents
2003-11-04 ’245 Patent Issued
2004-03-09 ’396 Patent Issued
2004-08-02 FDA Approved Truvada® for HIV-1 Treatment in Adults
2013-11-26 ’397 Patent Issued
2014-05-06 ’264 Patent Issued
2016-03-10 FDA Approved Truvada® Low Dosage Strengths
2016-10-04 ’036 Patent Issued
2017-08-29 ’181 Patent Issued
2018-12-03 Defendants Sent Paragraph IV Notice Letter to Plaintiffs
2019-01-15 Complaint Filed

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

U.S. Patent No. 6,642,245 - Antiviral Activity and Resolution of 2-Hydroxymethyl-5-(5-fluorocytosin-1-yl) -1,3-oxathiolane

The Invention Explained

  • Problem Addressed: The patent’s background section describes an urgent need for new pharmaceutical agents to treat HIV and Hepatitis B Virus (HBV) that are effective and have low toxicity to the host, addressing the limitations of existing therapies like AZT (Compl. ¶17; ’245 Patent, col. 1:36-2:68).
  • The Patented Solution: The invention provides a method for treating HIV by administering an effective amount of the compound emtricitabine (FTC). The patent discloses that FTC exhibits surprisingly high activity against HIV, including AZT-resistant strains, while demonstrating very low toxicity to human cells (’245 Patent, Abstract; col. 4:6-24). The chemical structure for the compound is provided in Figure 1 of the patent.
  • Technical Importance: The invention introduced a new chemical entity for antiviral therapy that offered a potent treatment option for HIV with a favorable safety profile compared to earlier-generation drugs (’245 Patent, col. 4:15-24).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶38).
  • Claim 1:
    • A method for treating HIV infection in humans
    • comprising administering an effective amount of [emtricitabine], or its physiologically acceptable salt,
    • optionally in a pharmaceutically acceptable carrier.
  • The complaint explicitly reserves the right to assert dependent claims 2, 4, 6, 7, and 8 (Compl. ¶38).

U.S. Patent No. 6,703,396 - Method of Resolution and Antiviral Activity of 1,3-Oxathiolane Nucleoside Enantiomers

The Invention Explained

  • Problem Addressed: The patent background explains that synthetic nucleosides like emtricitabine are often produced as a racemic mixture of two enantiomers (mirror-image molecules), only one of which is typically the more biologically active form. The problem is the need for an efficient method to separate, or resolve, these enantiomers to isolate the more potent version for therapeutic use (’396 Patent, col. 2:57-3:12).
  • The Patented Solution: The invention is a process for resolving these racemic mixtures using an enzyme that preferentially acts on one enantiomer. The patent specifically claims the substantially pure (-)-enantiomer of emtricitabine, which it discloses is significantly more potent against HIV than the (+)-enantiomer or the racemic mixture, and also claims pharmaceutical compositions containing this purified form (’396 Patent, Abstract; col. 4:43-52). The complaint provides the chemical structure of this specific enantiomer (Compl. ¶23).
  • Technical Importance: The invention provided a commercially viable method to produce a highly purified, more potent form of the key antiviral drug emtricitabine, improving its therapeutic index (’396 Patent, col. 4:48-52).

Key Claims at a Glance

  • The complaint asserts independent claims 1, 12, 14, and 22, among others (Compl. ¶49). Claims 1 (the compound) and 12 (the composition) are central.
  • Claim 1:
    • The (-)-enantiomer of cis-4-amino-5-fluoro-1-(2-hydroxymethyl-1,3-oxathiolane-5-yl)-(1H)-pyrimidin-2-one that is at least 95% free of the corresponding (+)-enantiomer.
  • Claim 12:
    • A pharmaceutical composition comprising an effective HIV treatment amount for humans of the (-)-enantiomer of a compound of cis-4-amino-5-fluoro-1-(2-hydroxymethyl-1,3-oxathiolane-5-yl)-(1H)-pyrimidin-2-one that is at least 95% free of the corresponding (+)-enantiomer,
    • in combination with a pharmaceutically acceptable carrier or diluent.
  • The complaint explicitly reserves the right to assert other claims, including dependent claims (Compl. ¶49).

U.S. Patent No. 8,592,397 - Compositions and Methods for Combination Antiviral Therapy

  • Issued: November 26, 2013 (Compl. ¶19).
  • Technology Synopsis: The patent addresses the need for chemically stable combination therapies for HIV. It claims a fixed-dose pharmaceutical tablet combining tenofovir disoproxil fumarate and emtricitabine with specific excipients (a binder, a disintegrant, and a lubricant) that exhibits less than 10% degradation of either active ingredient after 6 months under specified storage conditions (40° C./75% relative humidity) (Compl. ¶60).
  • Asserted Claims: At least Claim 1 is asserted (Compl. ¶60).
  • Accused Features: Defendants' proposed generic product is alleged to be a chemically stable, fixed-dose tablet containing 300 mg of tenofovir disoproxil fumarate and 200 mg of emtricitabine, with the required excipients and stability profile (Compl. ¶60).

U.S. Patent No. 8,716,264 - Compositions and Methods for Combination Antiviral Therapy

  • Issued: May 6, 2014 (Compl. ¶20).
  • Technology Synopsis: The patent claims a chemically stable fixed-dose combination of 300 mg of tenofovir disoproxil fumarate and 200 mg of emtricitabine. The claimed invention is defined by its stability, exhibiting less than 10% degradation of the active ingredients after six months when packaged and stored with a silica gel desiccant at 40° C./75% relative humidity (Compl. ¶71).
  • Asserted Claims: At least Claim 1 is asserted (Compl. ¶71).
  • Accused Features: Defendants' proposed generic product is alleged to be a chemically stable, fixed-dose tablet that meets the specific active ingredient and stability requirements of the claim (Compl. ¶71).

U.S. Patent No. 9,457,036 - Compositions and Methods for Combination Antiviral Therapy

  • Issued: October 4, 2016 (Compl. ¶21).
  • Technology Synopsis: This patent claims a fixed-dose combination tablet comprising 300 mg of tenofovir disoproxil fumarate, 200 mg of emtricitabine, and specific classes of excipients (binder, disintegrant, lubricant). It is further defined by a stricter stability requirement, exhibiting equal to or less than 5% degradation of the active ingredients after six months under specified storage conditions (Compl. ¶82).
  • Asserted Claims: At least Claim 1 is asserted (Compl. ¶82).
  • Accused Features: The complaint alleges that Defendants' proposed generic product is a fixed-dose tablet that contains the claimed active ingredients and excipients and will meet the claimed stability profile of ≤5% degradation (Compl. ¶82).

U.S. Patent No. 9,744,181 - Compositions and Methods for Combination Antiviral Therapy

  • Issued: August 29, 2017 (Compl. ¶22).
  • Technology Synopsis: The patent claims a fixed-dose combination tablet comprising 300 mg of tenofovir disoproxil fumarate and 200 mg of emtricitabine. The invention is defined by a stability requirement where the combination exhibits equal to or less than 5% degradation of the active ingredients after six months when packaged with a silica gel desiccant at 40° C./75% relative humidity (Compl. ¶93).
  • Asserted Claims: At least Claim 1 is asserted (Compl. ¶93).
  • Accused Features: The complaint alleges that Defendants' proposed product is a fixed-dose tablet that will contain the claimed active ingredients and meet the claimed stability profile (Compl. ¶93).

III. The Accused Instrumentality

Product Identification

The generic drug products that are the subject of Defendants' Abbreviated New Drug Application (ANDA) No. 212689 (Compl. ¶13, 31).

Functionality and Market Context

The accused products are tablets formulated for the treatment of HIV infection, containing the active ingredients emtricitabine and tenofovir disoproxil fumarate in four different dosage strengths: 100/150 mg, 133/200 mg, 167/250 mg, and 200/300 mg (Compl. ¶13). The complaint alleges these products are intended to compete directly with Gilead's branded Truvada® product upon receiving FDA approval (Compl. ¶13).

IV. Analysis of Infringement Allegations

U.S. Patent No. 6,642,245 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating HIV infection in humans The ANDA product will be labeled for and used to treat HIV infection in humans. ¶38 col. 6:5-13
comprising administering an effective amount of [emtricitabine], or its physiologically acceptable salt, The ANDA product will be administered to patients in an effective amount for treating HIV infection and contains emtricitabine. ¶38, ¶39 col. 1:39-43
optionally in a pharmaceutically acceptable carrier. The accused product is a tablet, which constitutes a pharmaceutically acceptable carrier for the active ingredients. ¶13, ¶31 col. 29:56-30:24

U.S. Patent No. 6,703,396 Infringement Allegations

Claim Element (from Independent Claim 12) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical composition comprising an effective HIV treatment amount for humans of the (-)-enantiomer of ... [emtricitabine] The product for which Defendants seek approval contains emtricitabine, which is the (-)-enantiomer, as the active ingredient for the treatment of HIV. ¶49 col. 4:43-52
that is at least 95% free of the corresponding (+)-enantiomer, The ANDA product is alleged to contain emtricitabine as the active ingredient, which, to be bioequivalent to the branded drug, would necessarily be the substantially pure (-)-enantiomer. ¶49 col. 18:8-13
in combination with a pharmaceutically acceptable carrier or diluent. The accused product is a tablet, which is a pharmaceutically acceptable carrier for the active ingredient. ¶13, ¶41 col. 14:48-51

Identified Points of Contention

  • Scope Questions: For the later formulation patents ('397, '264, '036, '181), a central dispute will involve the scope of terms such as "chemically stable" and the specific degradation percentage limitations (e.g., "equal to or less than 5% degradation"). The case will likely require detailed analysis of the stability testing data submitted in the ANDA to determine if the accused product falls within the claimed stability profiles.
  • Technical Questions: A key technical question for the formulation patents is whether Defendants' chosen excipients and manufacturing process result in a final product that meets the claimed stability requirements. For the method-of-treatment claims of the ’245 Patent, a question will be whether the Defendants' proposed product label will instruct users in a manner that directly encourages the performance of all steps of the claimed method, thereby supporting a finding of induced infringement.

V. Key Claim Terms for Construction

U.S. Patent No. 6,642,245

  • The Term: "effective amount"
  • Context and Importance: Practitioners may focus on this term because the question of whether the dosages in the accused product constitute an "effective amount" as understood in the patent is central to infringement of the method claim. A defendant could argue that the patent teaches a different effective range than what is provided in its generic product.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification discloses a wide range of potential dosages, such as "from about 1 to 50 mg/kg, preferably 1 to 20 mg/kg, of body weight per day, more generally 0.1 to about 100 mg per kilogram body weight" (’245 Patent, col. 30:8-13).
    • Evidence for a Narrower Interpretation: A party could argue that the term should be limited by the specific amounts shown to be effective in the patent's working examples, which provide concrete data on antiviral activity at specific concentrations (’245 Patent, col. 19:1-22:36, Examples 6-10).

U.S. Patent No. 9,457,036

  • The Term: "chemically stable"
  • Context and Importance: This term is a central limitation in the later-issued formulation patents. Its construction will determine the standard against which the accused product's stability is measured. Practitioners may focus on this term because infringement of the '397, '264, '036, and '181 Patents hinges on whether the accused product meets the claimed stability profile.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The '036 patent's parent, the '397 patent, defines "chemically stable" more generally as meaning "the two primary antiviral agents in combination are substantially stable to chemical degradation" and that one component "does not catalyzes or otherwise accelerate the acid decomposition of a second component" ('397 Patent, col. 3:43-55). A party might argue this broader definition informs the use of the term in later patents.
    • Evidence for a Narrower Interpretation: The claims themselves in the '036 and '181 patents explicitly define the required stability with a numerical limit: "wherein said pharmaceutical dosage form exhibits equal to or less than 5% degradation" under specified conditions (’036 Patent, col. 30:60-65). This language suggests the term is not open to broad interpretation but is instead explicitly defined by the quantitative limitation that follows.

VI. Other Allegations

Indirect Infringement

The complaint alleges Defendants will indirectly infringe by inducing infringement for all asserted patents. For the method patent (’245), this is based on the allegation that the accused product's label will instruct and encourage medical professionals and patients to administer the drug for the treatment of HIV infection (Compl. ¶38-39). For the composition patents, inducement is alleged based on the manufacture and proposed sale of tablets for use in treating HIV infection (e.g., Compl. ¶61, 72, 83, 94).

Willful Infringement

While the complaint does not use the word "willful," it alleges that Defendants had knowledge of each patent-in-suit as a result of filing a Paragraph IV certification (e.g., Compl. ¶39, 50, 61, 72, 83, 94). The prayer for relief requests that damages be trebled pursuant to 35 U.S.C. § 284, the statutory remedy for willful infringement (e.g., Compl. p. 25, ¶(s)-(x)).

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

  • A core issue will be one of technical fact and evidence: For the four later-issued formulation patents, the dispute will likely center on whether Zydus’s ANDA product, as formulated and manufactured, actually meets the quantitative stability limitations recited in the claims (e.g., exhibiting less than 10% or 5% degradation under specific conditions). This question will depend on factual discovery of Defendants' stability data and expert testimony on pharmaceutical formulation science.
  • A second key issue will be one of validity, specifically obviousness: Given that emtricitabine and tenofovir disoproxil fumarate were both known antiretroviral agents, a central question for the court will be whether it was obvious to a person of ordinary skill in the art to combine them into a single, fixed-dose tablet that possessed the specific chemical stability profiles claimed in the later patents, or if achieving this stability required an inventive step.
  • A final question may be one of claim interpretation: For the '264 Patent, the court will need to address the acknowledged typographical error in claim 1, which recites two different relative humidity values. The resolution of this inconsistency could impact the scope of the claim and the corresponding infringement analysis.