PATENT PROPHYLAXIS: EXPANDING ACCESS TO PREP THROUGH 28 U.S.C. [section] 1498.

• Author: Bell, Jonathan A.
• Position: United States v. Gilead Sciences, Inc.

TABLE OF CONTENTS Introduction 2058 I. Patent Infringement Litigation Is Unlikely to Expand Patient Access to PrEP 2063 A. The Development of Truvada for PrEP 2063 B. CDC's Patents-in-Suit 2064 C. Gilead's Underlying Patent 2066 D. The Shortcomings of Patent Infringement Litigation to Expand Drug Access 2067 II. A First Time for Everything: The Bayh-Dole Act 2071 A. How March-In Authority Works in Theory 2071 B. March-In Petitions Have Failed Repeatedly 2075 1. Ritonavir (2004) 2075 2. Ritonavir (2012) 2076 C. The Shortcomings of March-In Authority 2076 D. Paid-Up Licenses Are No Different 2078 III. The Path Forward: 28 U.S.C. S 1498 2080 A. Legislative History and Prior Use 2080 B. Strengths of S 1498 2083 C. Potential Drawbacks of S 1498 2087 Conclusion 2089 INTRODUCTION

On June 5, 1981, the United States Centers for Disease Control and Prevention (CDC) published a report detailing five cases of a rare lung infection in young, previously healthy, gay men living in Los Angeles. (1) This marked the first official report of acquired immunodeficiency syndrome (AIDS). (2) In the short time that followed, similar reports documented a rare form of cancer in gay men living in New York City and California. (3) By year's end, reports showed 337 individuals with AIDS in the United States; 130 of those individuals had died. (4) The end of the decade saw the number of cases in the United States exceed one hundred thousand and the number of AIDS-related deaths exceed fifty-nine thousand. (6)

AIDS is caused by the human immunodeficiency virus (HIV), a retrovirus that attacks CD4-positive T cells, causing a progressive depletion of the immune system. (6) After attaching to the cell surface and entering the cell, HIV integrates its genetic material into the host genome through a process known as reverse transcription. (7) This integration into host DNA makes HIV impossible to eradicate with current therapies. (8)

HIV remains a serious global health issue today. Since 1981, an estimated seventy-nine million people have become infected with HIV, and an estimated thirty-six million people have died from AIDS-related illnesses. (9) In 2020, thirty-eight million people were living with HIV globally, and 1.5 million people became newly infected with the virus. (10) In the United States alone, an estimated 1.2 million people are living with HIV/AIDS and, in 2019, an estimated 34,800 new HIV infections occurred. (11)

Today, medicine treats HIV as a chronic illness. (12) However, given the continued rate of new infections annually, there persists a critical need for effective methods to prevent the transmission and spread of the virus. (13) Pre-exposure prophylaxis (PrEP) is one such method. (14)

As its name suggests, PrEP is an HIV prevention medication that HIV-negative individuals take before exposure to the virus to reduce the risk of infection. (15) PrEP decreases the risk of HIV infection across multiple at-risk populations, including gay and bisexual men, (16) transgender women, (17) mixed-status couples (meaning only one partner has HIV), (18) and people who inject drugs. (19) As of publishing, there are currently three FDA-approved medications for PrEP: pill-based Truvada and Descovy, as well as injectable

Apretude. (20) Both Truvada and Descovy utilize fixed-dose combinations of the same two drugs--emtricitabine (21) and tenofovir (22)--manufactured and sold by the same company: Gilead Sciences. (23) Truvada is highly effective at preventing new HIV infections--up to 99 percent effective in individuals who take the medication daily. (24) Despite this proven efficacy, PrEP remains underutilized by and inaccessible to the most at-risk populations. CDC estimates show that 1.1 million people in the United States would benefit from access to PrEP, but since 2012 only 10 percent of adults with PrEP indications (20) have started taking the drug. (26) Of those who take the drug, the majority are white men who live in either the Northeast or West Coast and have sex with men. (27) Researchers and activists have pointed to one obvious cause for these large disparities in PrEP use across race, geographic region, and sex: the cost. (28)

Truvada for PrEP costs in excess of $1,900 a month in the United States. (29) Accordingly, the cost of preventing HIV infection for at-risk individuals is greater than sixty dollars a pill--sixty dollars a day. (30) Insurance should cover this cost, but the reality is more complicated. (31) The cost of Descovy, Gilead's new PrEP medication, is similarly high. (32) This exorbitant price stands in stark contrast to the generic version of Truvada sold internationally for six dollars a month--less than a quarter a day. (33)

These price discrepancies and subsequent calls from activists sparked a flurry of political and legal attention for PrEP access. Partially in response to this pressure, and as part of the former Trump administration's plan to end the HIV epidemic, (34) the administration initiated a rare patent infringement lawsuit against Gilead in November 2019. (35) In the suit, the government alleges that Gilead infringed on patents issued to the United States Department of Health and Human Services (HHS) and CDC. (36) According to court documents, Gilead has refused HHS's attempts to license these patents and collect royalties for years. (3) '

This approach greatly differs from Democratic lawmakers and PrEP activists' proposals to reduce the cost of PrEP and expand access to the drug. PrEP4All, one such activist group, has specifically called for the government to utilize march-in rights under section 203 of the Bayh-Dole Act or the paid-up license under section 202. (38) However, march-in rights have never been exercised in the forty years since the enactment of the Bayh-Dole Act. (39)

This Note argues that both approaches are wrong. Instead of utilizing patent infringement litigation to recover damages from Gilead or invoking a never-utilized provision of the Bayh-Dole Act to grant a manufacturing license, this Note argues that 28 U.S.C. [section] 1498, also known as "use without license," is the appropriate government action to rapidly expand access to PrEP and reduce costs to the individual patient.

Part I of this Note details the discovery of Truvada for PrEP and the ongoing patent infringement litigation brought by HHS, discusses the patents currently held by CDC and Gilead, and examines the shortcomings of infringement litigation as a means to expand access to the drug. Part II analyzes the mechanism of march-in rights under the Bayh-Dole Act and discusses two previously attempted applications for the HIV-management drug ritonavir to demonstrate why march-in rights will always fail to expand access to life-saving medications or reduce costs to consumers. Part III discusses the unique legal right conferred to the government under [section] 1498 and demonstrates why [section] 1498 is the correct course of action to expand access to PrEP. PrEP is a life-saving and life-altering medication. Patient access is an issue to address proactively--and prophylactically--through established intellectual property regimes.

1. PATENT INFRINGEMENT LITIGATION IS UNLIKELY TO EXPAND PATIENT ACCESS TO PREP

   In November 2019, the United States initiated a lawsuit against Gilead Sciences and its parent company Gilead Sciences Ireland for patent infringement concerning four patents for PrEP. (40) The government's complaint details a long history of drug development at CDC and repeatedly alleges that "Gilead's only contribution to CDC's patented research was providing samples of the drugs that CDC used for testing purposes." (41) The government alleges four counts of willful infringement of its patents. (42) In response, Gilead denies all infringement claims and raises several affirmative defenses and counterclaims. (43) As of publishing, the parties are completing discovery. (44) The trial is not set to occur until 2023. (45)

   1. The Development of Truvada for PrEP

      The government argues that years of experimentation at CDC, including the creation and development of novel animal modeling techniques for HIV transmission, are prerequisite to the discovery of emtricitabine and tenofovir for PrEP. (46) Results published by CDC in 2008 showed the first evidence that PrEP could effectively prevent the transmission of HIV in humans. (47) The study showed that in all test primates that received emtricitabine and tenofovir, either daily or immediately before exposure to SIV, (48) PrEP protected them from infection. (49) The five CDC scientists listed on the patentsin-suit authored this study. (110) In one published report, CDC researchers concluded that the high efficacy of this drug combination supported similar PrEP trials in humans; other researchers completed the first such trial two years later. (51)

      The Preexposure Prophylaxis Initiative (iPrEx) study randomly assigned 2,500 HIV-negative men or transgender women who have sex with men to receive the emtricitabine/tenofovir combination or a placebo. (52) Following the study's observation period, participants in the experimental group experienced a 44 percent reduction in the incidence of HIV infection. (53) Participants in the experimental group who adhered to the daily dose experienced a relative reduction in HIV-infection risk of 92 percent. (54) Based on this groundbreaking study and other subsequent trials, the FDA approved the use of emtricitabine/tenofovir as PrEP in 2012. (55)

   2. CDC's Patents-in-Suit

      Based off of this research, CDC obtained four patents: U.S. Patent Nos. 9,044,509 ('509), 9,579,333 ('333), 9,937,191 ('191), and 10,335,423 ('423). All four patents share the title "Inhibition of HIV Infection Through Chemoprophylaxis"; (56) list CDC scientists Walid Heneine, Thomas M. Folks, Robert Janssen, Ronald A. Otten, and Jose Gerardo Garcia Lerma as their inventors; and list the United States as assignee, via the Secretary of HHS. (57) The...