DCT
1:18-cv-00765
Gilead Sciences Inc v. Aurobindo Pharma Ltd
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Gilead Sciences, Inc. (Delaware) and Emory University (Georgia)
- Defendant: Aurobindo Pharma Ltd. (India) and Aurobindo Pharma USA, Inc. (Delaware)
- Plaintiff’s Counsel: Farnan LLP; Fitzpatrick, Cella, Harper & Scinto
- Case Identification: 1:18-cv-00765, D. Del., 05/18/2018
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Aurobindo Pharma USA, Inc. is a Delaware corporation.
- Core Dispute: Plaintiffs allege that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the HIV treatment Truvada® constitutes an act of infringement of two patents covering the compound emtricitabine and its method of use.
- Technical Context: The technology involves nucleoside analogue reverse-transcriptase inhibitors, a class of antiviral compounds central to the treatment of human immunodeficiency virus (HIV).
- Key Procedural History: This action was precipitated by Defendant’s submission of ANDA No. 21-1640 and its associated Paragraph IV certification notice letters, which advised Plaintiffs of Defendant's intent to market a generic drug prior to the expiration of the patents-in-suit. The complaint was filed within the 45-day statutory window following receipt of the notice letter, triggering a 30-month stay of FDA approval for the generic product.
Case Timeline
| Date | Event |
|---|---|
| 1990-02-01 | Earliest Priority Date for '245 and '396 Patents |
| 2003-11-04 | U.S. Patent No. 6,642,245 Issued |
| 2004-03-09 | U.S. Patent No. 6,703,396 Issued |
| 2004-08-02 | FDA Approval for Truvada® (adult formulation) |
| 2016-03-10 | FDA Approval for Truvada® (pediatric low dosage strengths) |
| 2018-04-05 | Aurobindo serves Paragraph IV Notice Letter |
| 2018-05-09 | Aurobindo serves amended Paragraph IV Notice Letter |
| 2018-05-18 | 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"
- Patent Identification: U.S. Patent No. 6,642,245, "Antiviral Activity and Resolution of 2-Hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane," issued November 4, 2003.
The Invention Explained
- Problem Addressed: The patent’s background section describes the need for new pharmaceutical agents to treat HIV and HBV infections, noting that these diseases had reached epidemic levels and existing treatments had limitations such as significant side effects and the potential for viral resistance (ʼ245 Patent, col. 1:41-52; col. 2:56-64).
- The Patented Solution: The invention provides a method for treating HIV infection by administering an effective amount of the compound 2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, also known as FTC or emtricitabine (ʼ245 Patent, Abstract; col. 4:8-18). The specification asserts that FTC exhibits "surprisingly high activity" against HIV alongside "very low host cell toxicity," a desirable combination for an antiviral therapeutic (ʼ245 Patent, col. 4:18-21).
- Technical Importance: The invention identified a novel therapeutic method using a nucleoside analogue with a potentially superior efficacy and safety profile compared to existing options for treating HIV (ʼ245 Patent, col. 4:18-24).
Key Claims at a Glance
- The complaint asserts independent claim 1 (Compl. ¶39).
- Essential elements of Claim 1:
- A method for treating HIV infection in humans
- comprising administering an effective amount of (-)-β-L-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, or its physiologically acceptable salt
- optionally in a pharmaceutically acceptable carrier
- The complaint alleges infringement of dependent claims 2, 4, 6, 7, and 8 (Compl. ¶39).
U.S. Patent No. 6,703,396 - "Method of Resolution and Antiviral Activity of 1,3-Oxathiolane Nucleoside Enantiomers"
- Patent Identification: U.S. Patent No. 6,703,396, "Method of Resolution and Antiviral Activity of 1,3-Oxathiolane Nucleoside Enantiomers," issued March 9, 2004.
The Invention Explained
- Problem Addressed: The patent addresses a common challenge in pharmaceutical manufacturing: synthetic nucleosides are often produced as racemic mixtures containing multiple stereoisomers (enantiomers), only one of which may possess the desired therapeutic activity (ʼ396 Patent, col. 2:55-65). Developing a cost-effective, scalable process to resolve these mixtures and isolate the active enantiomer is a significant technical hurdle (ʼ396 Patent, col. 3:15-22).
- The Patented Solution: The invention claims the specific, isolated (-) enantiomer of the FTC compound (emtricitabine) and its pharmaceutically acceptable salts and esters (ʼ396 Patent, Claims 1-2). The specification also describes a process for resolving the racemic mixture using enzymes that preferentially catalyze a reaction in one of the enantiomers, enabling its separation (ʼ396 Patent, Abstract; Fig. 2).
- Technical Importance: The invention provided the purified, therapeutically active form of a potent antiviral compound, a critical step for its development as a safe and effective drug (ʼ396 Patent, Abstract).
Key Claims at a Glance
- The complaint asserts independent claims 1 and 2 (Compl. ¶50). Claim 2 is specifically quoted.
- Essential elements of Claim 2:
- (-)-Cis-4-amino-5-fluoro-1-(2-hydroxymethyl-1,3-oxathiolane-5-yl)-(1H)-pyrimidin-2-one [emtricitabine]
- or a pharmaceutically acceptable salt, ester or salt of an ester thereof
- The complaint alleges infringement of dependent claims 3-7, 13, 15, and 16 (Compl. ¶50).
III. The Accused Instrumentality
Product Identification
- Aurobindo’s proposed generic drug product that is the subject of Abbreviated New Drug Application (ANDA) No. 21-1640 (Compl. ¶19, ¶31).
Functionality and Market Context
- The accused product is a tablet containing a combination of emtricitabine and tenofovir disoproxil fumarate, offered in several dosage strengths (Compl. ¶19). The complaint provides the chemical structure of emtricitabine, the active ingredient at issue (Compl. ¶25). The product is intended for the treatment of HIV-1 infection and, if approved, would compete directly with Plaintiffs' branded product, Truvada® (Compl. ¶19).
IV. Analysis of Infringement Allegations
'245 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for treating HIV infection in humans | Aurobindo’s ANDA product, if approved, will be labeled for and used to treat HIV infection in humans. | ¶39 | col. 32:1-2 |
| comprising administering an effective amount of (-)-β-L-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, or its physiologically acceptable salt, | The proposed generic product contains emtricitabine, the compound recited in the claim, and will be administered to patients in an amount effective for treating HIV infection. | ¶39, ¶40 | col. 32:3-7 |
| optionally in a pharmaceutically acceptable carrier. | The proposed product is a tablet formulation, which includes pharmaceutically acceptable carriers. | ¶39 | col. 32:8 |
'396 Patent Infringement Allegations
| Claim Element (from Independent Claim 2) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| (-)-Cis-4-amino-5-fluoro-1-(2-hydroxymethyl-1,3-oxathiolane-5-yl)-(1H)-pyrimidin-2-one | Aurobindo’s ANDA product contains emtricitabine as an active ingredient, which is the compound recited in the claim. | ¶50 | col. 18:26-29 |
| or a pharmaceutically acceptable salt, ester or salt of an ester thereof. | The product for which Aurobindo seeks approval is a pharmaceutical formulation that will contain emtricitabine or a pharmaceutically acceptable salt thereof. | ¶50 | col. 18:27-29 |
Identified Points of Contention
- '245 Patent (Method Claim): Infringement of this method-of-treatment claim hinges on a theory of inducement. A key question for the court will be whether the proposed label for Aurobindo's generic product will instruct or encourage medical professionals and patients to administer the drug in a way that performs all steps of the claimed method (Compl. ¶40).
- '396 Patent (Composition Claim): The complaint alleges that Aurobindo's Paragraph IV notice letter asserts invalidity for the claims of the '396 Patent but does not allege non-infringement of claims 1-7, 11, 13, 15, and 17, which include the asserted independent claims (Compl. ¶45, ¶46). This suggests the central dispute regarding the '396 Patent may be over its validity rather than factual questions of infringement.
V. Key Claim Terms for Construction
- Term: "an effective amount" (from '245 Patent, Claim 1)
- Context and Importance: This term connects the act of administration to the therapeutic outcome of treating HIV. Its construction is critical for determining the scope of the method claim. Practitioners may focus on this term because its definition will determine whether the specific dosages proposed in Aurobindo's ANDA fall within the patented method.
- Intrinsic Evidence for a Broader Interpretation: The specification discloses a wide dosage range, stating that a preferred dose "will be in the range from about 1 to 50 mg/kg... of body weight per day," and notes that the precise dose depends on various factors, which could support a flexible interpretation ('245 Patent, col. 30:45-53).
- Intrinsic Evidence for a Narrower Interpretation: The specification provides specific data from in vitro and in vivo studies showing efficacy at particular concentrations and dosages (e.g., '245 Patent, Table 3; Table 6). A party could argue these examples inform and potentially limit the meaning of what constitutes an "effective amount."
- Term: "(-)-enantiomer...that is at least 95% free of the corresponding (+)-enantiomer" (from '396 Patent, Claim 1)
- Context and Importance: This term defines the purity of the claimed compound. Its construction is important because infringement may depend on whether Aurobindo's product meets this specific purity threshold. Practitioners may focus on this term to determine if there is a factual dispute over the isomeric purity of the accused product.
- Intrinsic Evidence for a Broader Interpretation: The claim sets a clear numerical floor (95%), suggesting any product meeting or exceeding this purity level infringes. The term is part of a composition claim, which is typically defined by its structure and properties, not its method of manufacture.
- Intrinsic Evidence for a Narrower Interpretation: The specification describes specific enzymatic resolution processes used to achieve high enantiomeric excess ('396 Patent, Example 2). While a weak position, a party might argue that the term's meaning is tied to the outcomes achievable through the disclosed methods, or that measurement methodologies could introduce ambiguity.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Aurobindo will induce infringement of the '245 Patent method claim by labeling its product for the treatment of HIV, thereby encouraging physicians and patients to perform the patented method (Compl. ¶40). For the '396 Patent, the complaint alleges Aurobindo will aid and abet the manufacture of infringing tablets (Compl. ¶51).
- Willful Infringement: The complaint does not use the term "willful," but it requests trebled damages, the statutory remedy for willful or egregious infringement (Compl. ¶12(g)-(h)). The alleged basis for knowledge of the patents is Aurobindo's ANDA filing and its service of Paragraph IV notice letters on the Plaintiffs prior to the suit (Compl. ¶40, ¶51).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of validity vs. infringement. For the '396 patent, which claims the emtricitabine compound itself, the dispute may center on Aurobindo's anticipated challenge to the patent's validity, as the complaint suggests Aurobindo has not contested that its product meets the claim's structural limitations.
- A second key issue will be one of induced infringement. For the '245 patent, which claims a method of treatment, the case will likely turn on whether the evidence, particularly the language of Aurobindo’s proposed product label, is sufficient to prove that Aurobindo intended for and took affirmative steps to encourage direct infringement by end-users.
- Finally, a potential question of claim scope could arise concerning the term "an effective amount" in the '245 patent. The court's interpretation of this term will define the boundaries of the patented method and determine whether the specific dosages of Aurobindo's proposed product fall within them.