United States v. Gilead Sciences Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: The United States of America (Washington, D.C.)
  • Defendant: Gilead Sciences, Inc. (Delaware); Gilead Sciences Ireland UC (Ireland)
  • Plaintiff’s Counsel: U.S. Department of Justice
• Case Identification: 1:19-cv-02103, D. Del., 11/06/2019
• Venue Allegations: Venue is alleged to be proper as to Gilead Sciences, Inc. because it is a Delaware corporation, and as to Gilead Sciences Ireland UC because it is an alien defendant.
• Core Dispute: Plaintiff alleges that Defendant’s sale and promotion of its Truvada® and Descovy® products for pre-exposure prophylaxis (PrEP) induces infringement of four government-owned patents related to methods of preventing HIV infection.
• Technical Context: The technology concerns the use of a two-drug antiretroviral combination therapy, taken prior to potential viral exposure, to prevent the establishment of HIV in uninfected individuals.
• Key Procedural History: The complaint alleges that after years of unsuccessful licensing negotiations, Defendant filed inter partes review (IPR) petitions challenging the validity of all four patents-in-suit at the U.S. Patent and Trademark Office in August 2019, approximately three months before this complaint was filed.

Case Timeline

Date	Event
2004-01-01	FDA approves Truvada® for HIV treatment
2005-05-01	CDC-designed animal experiments for PrEP begin
2006-02-03	Patent Priority Date ('509, '333, '191, '423 Patents)
2006-02-05	First public presentation of CDC's PrEP data at CROI conference
2012-07-01	FDA approves Truvada® for HIV pre-exposure prophylaxis (PrEP)
2015-06-02	U.S. Patent No. 9,044,509 issues
2016-04-01	FDA approves Descovy® for HIV treatment
2017-02-28	U.S. Patent No. 9,579,333 issues
2018-04-10	U.S. Patent No. 9,937,191 issues
2019-07-02	U.S. Patent No. 10,335,423 issues
2019-08-21	Gilead files IPR petitions challenging '509 and '333 patents
2019-08-23	Gilead files IPR petitions challenging '191 and '423 patents
2019-10-03	FDA approves Descovy® for HIV pre-exposure prophylaxis (PrEP)
2019-11-06	Complaint filed

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

U.S. Patent No. 9,044,509 - "Inhibition of HIV Infection through Chemoprophylaxis," issued June 2, 2015

The Invention Explained

• Problem Addressed: The patent background describes the global spread of HIV and the lack of an effective pre-exposure prophylactic regimen to prevent an individual from developing a self-propagating infection after an initial exposure (Compl. ¶77; ’509 Patent, col. 1:35-54). Previous efforts with single-drug regimens had proven only partially protective (Compl. ¶¶89-90).
• The Patented Solution: The invention is a process for protecting a primate host from HIV by administering a specific two-drug combination—a nucleoside reverse transcriptase inhibitor (emtricitabine, or FTC) and a nucleotide reverse transcriptase inhibitor (tenofovir or its prodrug, tenofovir disoproxil fumarate, or TDF)—prior to viral exposure (’509 Patent, Abstract; col. 2:20-31). This pre-exposure administration is designed to block the virus from establishing a self-replicating infection in the host (Compl. ¶¶94-95).
• Technical Importance: This specific two-drug combination demonstrated an unexpectedly high efficacy in animal models, overcoming the insufficient protection offered by prior TDF-only regimens and establishing a new standard for HIV prevention research (Compl. ¶¶91, 115).

Key Claims at a Glance

• The complaint asserts independent claims 1 and 12, as well as dependent claim 13 (Compl. ¶282).
• Independent Claim 1: A process of protecting a primate host from a self-replicating infection by an immunodeficiency retrovirus comprising:
  • selecting a primate host not infected with the immunodeficiency retrovirus, and
  • administering directly to an uninfected primate host a combination comprising a pharmaceutically effective amount of emtricitabine; and a pharmaceutically effective amount of tenofovir or tenofovir disoproxil fumarate,
  • wherein the combination is administered orally prior to an exposure of the primate host to the immunodeficiency retrovirus.
• Independent Claim 12: A process for inhibiting establishment of a human immunodeficiency virus self-replicating infection in a human, comprising:
  • selecting an uninfected human that does not have the self-replicating infection; and
  • administering to the uninfected human a combination comprising a pharmaceutically effective amount of emtricitabine; and a pharmaceutically effective amount of tenofovir or tenofovir ester;
  • thereby inhibiting the establishment of the self-replicating infection with the immunodeficiency virus in the human, wherein the combination is administered orally.

U.S. Patent No. 9,579,333 - "Inhibition of HIV Infection through Chemoprophylaxis," issued February 28, 2017

The Invention Explained

• Problem Addressed: The ’333 Patent shares a specification with the ’509 Patent and addresses the same problem: the absence of an effective and safe pre-exposure prophylaxis regimen to prevent HIV infection (’333 Patent, col. 1:35-54).
• The Patented Solution: The patented solution is materially the same as that of the ’509 Patent, claiming a method of preventing HIV infection through pre-exposure administration of a combination of emtricitabine and tenofovir (or a prodrug). The claims of the ’333 Patent, however, recite different administration routes beyond only oral administration (’333 Patent, Abstract; col. 13:53-59).
• Technical Importance: The technical importance is the same as described for the ’509 Patent, based on the same underlying research demonstrating high prophylactic efficacy (Compl. ¶115).

Key Claims at a Glance

• The complaint asserts independent claims 1 and 12, as well as dependent claim 13 (Compl. ¶291).
• Independent Claim 1: A process of protecting a primate host from a self-replicating infection by an immunodeficiency retrovirus comprising:
  • selecting a primate host not infected with the immunodeficiency retrovirus, and
  • administering directly to an uninfected primate host a combination comprising emtricitabine and tenofovir or tenofovir disoproxil fumarate,
  • wherein the pharmaceutically effective amount of each component is administered orally, subcutaneously or vaginally, and
  • wherein the combination is administered prior to the exposure of the primate host.
• Independent Claim 12: A process for inhibiting establishment of a human immunodeficiency virus self-replicating infection in a human, comprising:
  • selecting an uninfected human that does not have the self-replicating infection; and
  • administering to the uninfected human a combination comprising emtricitabine and tenofovir or tenofovir disoproxil fumarate,
  • wherein the pharmaceutically effective amount of each component is administered orally, subcutaneously or vaginally.

Multi-Patent Capsule: U.S. Patent No. 9,937,191

• Patent Identification: U.S. Patent No. 9,937,191, "Inhibition of HIV Infection through Chemoprophylaxis," issued April 10, 2018 (Compl. ¶212).
• Technology Synopsis: Stemming from the same disclosure as the ’509 Patent, this patent covers the same method of using a two-drug combination (FTC and tenofovir/TDF) for pre-exposure prophylaxis to prevent HIV infection (Compl. ¶196). The claims of the ’191 Patent add the limitation that the drug combination is "administered orally in tablet form" (’191 Patent, col. 12:7-8).
• Asserted Claims: Independent claims 1 and 13 (Compl. ¶299).
• Accused Features: The marketing and sale of Truvada® for PrEP, which is an oral tablet containing FTC and TDF, is alleged to induce infringement (Compl. ¶¶299-300).

Multi-Patent Capsule: U.S. Patent No. 10,335,423

• Patent Identification: U.S. Patent No. 10,335,423, "Inhibition of HIV Infection through Chemoprophylaxis," issued July 2, 2019 (Compl. ¶217).
• Technology Synopsis: Sharing the same disclosure as the prior patents-in-suit, this patent covers the same core method of pre-exposure prophylaxis against HIV (Compl. ¶196). The claims of the ’423 Patent are broader with respect to the tenofovir component, reciting "tenofovir or a tenofovir prodrug" (’423 Patent, col. 13:8-9). This language explicitly covers a broader class of drugs than the earlier patents that specified only tenofovir or TDF.
• Asserted Claims: Independent claims 1 and 12 (Compl. ¶307).
• Accused Features: The sale and promotion of both Truvada® (containing TDF, a tenofovir prodrug) and Descovy® (containing TAF, another tenofovir prodrug) for PrEP are alleged to induce infringement (Compl. ¶¶307-309).

III. The Accused Instrumentality

Product Identification

Truvada® and Descovy® (Compl. ¶6).

Functionality and Market Context

• Truvada® is a once-daily oral tablet containing a fixed-dose combination of 200 mg of emtricitabine (FTC) and 300 mg of tenofovir disoproxil fumarate (TDF) (Compl. ¶48, 257). Descovy® is a once-daily oral tablet containing 200 mg of FTC and 25 mg of tenofovir alafenamide (TAF), a different prodrug of tenofovir (Compl. ¶¶55-56, 273).
• Both products are marketed and sold by Gilead under the indication for use as PrEP, in combination with safer sex practices, to reduce the risk of sexually acquired HIV-1 in at-risk adults (Compl. ¶¶253, 258, 269, 273). The complaint alleges that Gilead provides extensive instructions to healthcare providers and patients on using these products for PrEP through prescribing information, training guides, and patient agreement forms (Compl. ¶¶259-260, 272).
• The complaint alleges that sales of Truvada® for PrEP are a significant source of revenue for Gilead, totaling approximately $6.7 billion in the U.S. since mid-2015, and that Gilead is actively working to transition patients to the newer Descovy® product (Compl. ¶¶255, 271). A figure in the complaint depicts the experimental protocol from the CDC's research, which tested the daily oral FTC/TDF regimen (Group 2) that corresponds to the accused use of Truvada® (Compl. p. 29).

IV. Analysis of Infringement Allegations

'509 Patent Infringement Allegations

Claim Element (from Independent Claim 12)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
A process for inhibiting establishment of a human immunodeficiency virus self-replicating infection ... in a human, comprising: (a) selecting an uninfected human that does not have the self-replicating infection; and	Defendant instructs healthcare providers to confirm a patient's HIV-negative status before initiating PrEP and to conduct regular repeat testing.	¶260	col. 13:17-23
(b) administering to the uninfected human a combination comprising: i. a pharmaceutically effective amount of emtricitabine; and	Defendant markets, sells, and provides instructions for patients to take a once-daily oral tablet of Truvada® (200mg FTC / 300mg TDF) or Descovy® (200mg FTC / 25mg TAF).	¶¶257-258, 273	col. 13:24-27
ii. a pharmaceutically effective amount of tenofovir or tenofovir ester;	Truvada® contains TDF, and Descovy® contains TAF. The complaint alleges that both TDF and TAF are tenofovir esters.	¶202	col. 13:28
wherein the combination is administered orally.	Defendant's prescribing information for both Truvada® and Descovy® for PrEP specifies a once-daily oral tablet.	¶¶258, 273	col. 13:31-32

Identified Points of Contention

• Scope Questions: A primary question for infringement of some claims will be one of definitional scope. For instance, does the phrase "tenofovir or tenofovir disoproxil fumarate" in Claim 1 of the ’509 Patent read on the active ingredient tenofovir alafenamide (TAF) in Descovy®? The specific recitation of TDF may suggest the exclusion of other tenofovir prodrugs from that claim's scope. Conversely, Claim 12 of the same patent uses the broader term "tenofovir ester," which the complaint alleges covers TAF, raising the question of how these different claim scopes will be applied to the different accused products. A graph in the complaint shows the results of the CDC's experiments, demonstrating the high efficacy of the FTC/TDF combination (Group 2) compared to untreated controls (Compl. p. 30).
• Technical Questions: The case is based on a theory of induced infringement. A key factual question will be whether Gilead's marketing, labeling, and training materials provide specific instructions or encouragement to healthcare providers and patients to perform all steps of the patented methods, thus demonstrating the requisite intent for inducement under 35 U.S.C. § 271(b).

V. Key Claim Terms for Construction

"prior to an exposure" / "prior to a potential exposure"

• Context and Importance: This term is central to the invention's identity as a pre-exposure prophylaxis, distinguishing it from post-exposure treatments. Its construction will define the temporal relationship required between administration of the drug and the risk of infection. Practitioners may focus on this term to delineate the boundaries between the patented method and other therapeutic approaches.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The specification's description of a "regime of regular daily doses" and the goal of maintaining a "therapeutic level" of the drugs in the host suggests "prior to exposure" covers a continuous state of protection achieved through an ongoing regimen, rather than a single act before an imminent exposure event (’509 Patent, col. 5:45-54).
  • Evidence for a Narrower Interpretation: The specification also contemplates a single dose administered "within 12 hours prior to retroviral exposure and still more preferably often within 2 hours," which could be used to argue for a more temporally limited construction in certain contexts (’509 Patent, col. 5:31-34).

"tenofovir ester" (from ’509 Patent, Claim 12)

• Context and Importance: The construction of this term is critical to determining whether Descovy® infringes the ’509 Patent. Descovy® contains tenofovir alafenamide (TAF), which is a different chemical entity than the tenofovir disoproxil fumarate (TDF) found in Truvada®. Practitioners may focus on this term because it represents a key distinction between the accused products and the scope of different asserted claims.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The term "tenofovir ester" is a standard chemical classification. The plain and ordinary meaning of the term would encompass any compound that is an ester of tenofovir, which would include both TDF and TAF. The complaint explicitly alleges that TAF is a tenofovir ester (Compl. ¶202).
  • Evidence for a Narrower Interpretation: A defendant may argue that, in the context of the patent, the term should be limited to the specific ester disclosed and tested, TDF. The use of the narrower phrase "tenofovir or tenofovir disoproxil fumarate" in Claim 1 of the same patent could be cited as evidence that the patentee knew how to be specific and intended a broader meaning for "tenofovir ester" in Claim 12; however, it could also create ambiguity for a fact-finder.

VI. Other Allegations

Indirect Infringement

The complaint's theory of liability is exclusively induced infringement under 35 U.S.C. § 271(b). It alleges Gilead instructs and encourages infringement by healthcare providers and patients through its FDA-approved product labeling, prescribing information, promotional materials, and training guides that explicitly detail the administration of Truvada® and Descovy® for PrEP (Compl. ¶¶256-261, 283-284, 292, 300, 308-309).

Willful Infringement

The complaint alleges willfulness based on both pre- and post-suit knowledge. It alleges Gilead was aware of the government's patent application as early as 2008 through scientific publications it reviewed (Compl. ¶¶131, 275). It further alleges direct notice of the pending and issued patents via repeated licensing invitations beginning in 2014, which Gilead allegedly ignored or refused (Compl. ¶¶234, 238-241).

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

• A central issue will be one of validity: can the government's patents withstand Gilead's asserted defense that the claimed method was obvious in light of prior knowledge in the field? The case will likely involve a detailed examination of the state of the art before the patent's 2006 priority date, focusing on whether the high efficacy of the specific FTC/TDF combination for PrEP was an unexpected result that solved a known problem.
• A second core issue will be one of claim scope and infringement: particularly concerning the newer Descovy® product, can the claims of the earlier patents be construed to cover the tenofovir alafenamide (TAF) formulation? The dispute will turn on whether terms like "tenofovir ester" are given their plain chemical meaning or are limited by the patent's specific disclosures.
• A key evidentiary question will be one of intent for inducement: what evidence demonstrates that Gilead, by marketing and selling its PrEP drugs, specifically intended for doctors and patients to perform the patented methods, particularly during the period of alleged willful infringement after receiving notice of the patents?