DCT
1:23-cv-00775
Gilead Sciences Inc v. Apotex Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Gilead Sciences, Inc. (Delaware)
- Defendant: Apotex Inc. (Canada) and Apotex Corp. (Delaware)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
- Case Identification: Gilead Sciences, Inc. v. Apotex Inc. and Apotex Corp., 1:23-cv-00775, D. Del., 07/14/2023
- Venue Allegations: Venue is alleged to be proper for Apotex Corp. because it is a Delaware corporation and for Apotex Inc. because it is a foreign corporation subject to personal jurisdiction in the district.
- Core Dispute: Plaintiff alleges that Defendants’ submission of an Abbreviated New Drug Application (ANDA) to market a generic version of the HIV treatment GENVOYA® constitutes an act of infringement of two patents covering a specific crystalline salt form of the active ingredient tenofovir alafenamide.
- Technical Context: The technology concerns a specific hemifumarate salt form of tenofovir alafenamide, an antiviral prodrug, which offers improved stability and purity properties critical for pharmaceutical manufacturing and commercialization.
- Key Procedural History: The complaint states that this action was filed in response to a notice letter dated June 1, 2023, in which Apotex provided a Paragraph IV certification against the patents-in-suit as part of its ANDA filing. This suit, filed within 45 days of Gilead's receipt of the notice, triggers a statutory 30-month stay of FDA approval for Apotex's generic product.
Case Timeline
| Date | Event |
|---|---|
| 2011-08-16 | Priority Date for '065 and '769 Patents |
| 2014-06-17 | U.S. Patent No. 8,754,065 Issued |
| 2016-03-29 | U.S. Patent No. 9,296,769 Issued |
| 2023-06-01 | Apotex sends GENVOYA Notice Letter to Gilead |
| 2023-06-02 | Gilead receives Apotex's GENVOYA Notice Letter |
| 2023-07-14 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 8,754,065, Tenofovir Alafenamide Hemifumarate, Issued June 17, 2014
The Invention Explained
- Problem Addressed: The patent addresses the need for improved forms of phosphonate nucleotide analog prodrugs useful in antiviral therapy (Compl. Ex. A, '065 Patent, col. 1:15-18). The specification highlights challenges with a prior monofumarate form, including the presence of a "major diastereomeric impurity" and lower thermal stability ('065 Patent, col. 5:1-5, col. 11:40-48).
- The Patented Solution: The patent discloses and claims a specific crystalline salt form of tenofovir alafenamide, "tenofovir alafenamide hemifumarate" ('065 Patent, Abstract). This form is characterized by a specific stoichiometric ratio of approximately 0.5 moles of fumaric acid to one mole of tenofovir alafenamide ('065 Patent, col. 2:37-43). The patent asserts this hemifumarate form has advantages over the prior monofumarate form, including "improved thermodynamic and chemical stability," "superior process reproducibility," and a "higher melting point" ('065 Patent, col. 5:6-10).
- Technical Importance: Developing a stable, highly pure, and reproducible crystalline form of an active pharmaceutical ingredient is critical for ensuring drug product quality, safety, and shelf-life during large-scale manufacturing and distribution ('065 Patent, col. 10:50-60).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 and dependent claim 17 (Compl. ¶¶ 43-44).
- Independent Claim 1:
- Tenofovir alafenamide hemifumarate.
- The complaint reserves the right to assert additional claims (Compl. ¶42).
U.S. Patent No. 9,296,769, Tenofovir Alafenamide Hemifumarate, Issued March 29, 2016
The Invention Explained
- Problem Addressed: This patent, a continuation of the application that led to the '065 patent, further addresses the issue of purity. Specifically, it focuses on controlling for the presence of "tenofovir alafenamide monofumarate" as an impurity within a composition of the desired hemifumarate form (Compl. Ex. B, '769 Patent, col. 7:45-52).
- The Patented Solution: The invention claims a pharmaceutical composition that contains the tenofovir alafenamide hemifumarate salt but is defined by a specific purity threshold. The claimed composition must comprise "less than about 5% by weight of tenofovir alafenamide monofumarate" ('769 Patent, Claim 1). The specification provides data showing the hemifumarate form is exceptionally capable of purging diastereomeric impurities compared to the monofumarate form ('769 Patent, col. 10:35-50).
- Technical Importance: Controlling the level of specific process-related impurities is a key regulatory and safety requirement in pharmaceutical development, and a manufacturing process that yields a final product meeting such purity specifications is highly valuable.
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 and dependent claim 10 (Compl. ¶¶ 79-80).
- Independent Claim 1:
- A composition comprising tenofovir alafenamide hemifumarate,
- wherein the composition comprises less than about 5% by weight of tenofovir alafenamide monofumarate.
- The complaint reserves the right to assert additional claims (Compl. ¶78).
III. The Accused Instrumentality
Product Identification
The accused instrumentality is Apotex’s proposed generic version of GENVOYA®, referred to as the "GENVOYA ANDA Product" (Compl. ¶8).
Functionality and Market Context
The GENVOYA ANDA Product is described as a four-drug combination tablet intended as a complete regimen for the treatment of HIV-1 infection (Compl. ¶37). The filing of the ANDA signifies that Apotex represents its product has the same active ingredients, dosage form, and strength as Gilead's branded GENVOYA® and is bioequivalent to it (Compl. ¶36). The complaint alleges that this proposed product contains the patented tenofovir alafenamide hemifumarate as one of its active ingredients (Compl. ¶¶ 43, 79).
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
’065 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| Tenofovir alafenamide hemifumarate. | The complaint alleges, on information and belief, that "the GENVOYA ANDA Product contains tenofovir alafenamide hemifumarate." | ¶43 | col. 2:30-36 |
Identified Points of Contention:
- Factual Question: The central dispute for the '065 Patent appears to be factual rather than a matter of claim construction. The primary question is whether Apotex's proposed generic product, as described in its confidential ANDA submission, actually contains the specific "tenofovir alafenamide hemifumarate" crystalline salt form claimed in the patent.
’769 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A composition comprising tenofovir alafenamide hemifumarate, | The complaint alleges that "the GENVOYA ANDA Product contains tenofovir alafenamide hemifumarate..." | ¶79 | col. 7:47-49 |
| wherein the composition comprises less than about 5% by weight of tenofovir alafenamide monofumarate. | The complaint alleges that in the accused product, "the composition comprises less than about 5% by weight of tenofovir alafenamide monofumarate..." | ¶79 | col. 7:49-52 |
Identified Points of Contention:
- Technical Question: Similar to the '065 Patent, a key question is evidentiary: what is the purity profile of the Apotex product? The infringement analysis hinges on whether the product contains the monofumarate impurity at a level below the claimed threshold.
- Scope Question: A potential legal dispute may arise over the scope of the term "about 5%." Whether the accused product infringes could depend on the degree of numerical flexibility the court affords the word "about."
V. Key Claim Terms for Construction
For the '065 Patent, the single claim limitation "Tenofovir alafenamide hemifumarate" is a precise chemical term. The dispute will likely focus on the factual question of whether the accused product meets this definition, rather than on the construction of the term itself.
For the '769 Patent, the following term may be critical:
- The Term: "about 5% by weight"
- Context and Importance: This term sets the upper boundary for a specific impurity, the monofumarate form. Infringement of claim 1 of the ’769 Patent directly depends on whether the accused product's composition falls within this limitation. Practitioners may focus on this term because if Apotex's product contains the monofumarate impurity at a level close to 5%, the construction of "about" could determine the outcome of the infringement analysis.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patentee’s use of the word "about" suggests that the claimed value is not meant to be a strict, literal endpoint and that some deviation is contemplated ('769 Patent, Claim 1). This is consistent with the general understanding of the term in patent law.
- Evidence for a Narrower Interpretation: The specification includes an example where the crystallization process reduced an impurity from 10.0% to 0.65%, a level significantly below 5% ('769 Patent, Table 2). A party could argue this demonstrates that the invention's true advance lies in substantial purification, potentially counseling against a broad reading of "about." Furthermore, dependent claims recite narrower ranges of "less than about 1%" and "less than about 0.5%," providing context for the numerical limitations in the patent ('769 Patent, Claims 2-3).
VI. Other Allegations
- Indirect Infringement: The complaint alleges induced infringement under 35 U.S.C. § 271(b). The basis for this allegation is Apotex's "Proposed Label" for its generic product, which will allegedly instruct physicians to administer the product for the treatment of HIV-1, thereby encouraging an infringing use (Compl. ¶¶ 61-64, 97-100).
- Willful Infringement: The complaint does not explicitly plead willfulness. However, it alleges that Apotex has "actual knowledge" of the patents-in-suit and became aware of them "no later than the filing of its GENVOYA ANDA" (Compl. ¶¶ 57-58, 93-94). These allegations of pre-suit knowledge, combined with a prayer for relief seeking a finding that the case is "exceptional" under 35 U.S.C. § 285, lay the groundwork for a potential future claim of willful infringement or a request for enhanced damages.
VII. Analyst’s Conclusion: Key Questions for the Case
The resolution of this ANDA litigation will likely depend on the answers to two primary questions:
A central issue will be one of evidentiary proof: what does the chemistry, manufacturing, and controls (CMC) section of Apotex’s confidential ANDA filing reveal about its proposed product? The case turns on the factual questions of whether the product contains the specific "tenofovir alafenamide hemifumarate" crystalline salt and whether its purity profile meets the "less than about 5%" monofumarate limit of the '769 Patent.
A secondary but potentially dispositive issue may be one of definitional scope: if the accused product’s impurity level is near the claimed threshold, how will the court construe the term "about 5% by weight"? The degree of flexibility granted to this term could be decisive in the infringement analysis for the '769 Patent.