US Federal rights in patents on Probuphine, to treat opioid addiction

Probuphine is an expensive medication used to treat opioid dependence by providing maintenance treatment and lessening withdrawal symptoms. The U.S. federal government also has considerable leverage over the pricing of this product, because of the federal funding of the the research that lead to the sole Orange Book patent on the product, and phase 3 trials that were used the register the product.

Probuphine consists of four rods which are implanted under the skin of a patient’s arm. These four rods work for six months to provide a continuous supply of buprenorphine, a partial opioid agonist, into the patient’s system. While buprenorphine is available in generic form, Probuphine is patented. The medication is protected by only one patent, for the delivery mechanism.

The benefits of an implant are numerous. While buprenorphine is available as a tablet and a sublingual form, these forms require frequent dosage and compliance from a patient. The subdermal implant requires only a visit to a doctor’s office every six months. Additionally, the implant is more difficult to abuse or resell than other forms of buprenorphine. One study in the Journal of the American Medical Association found that patients receiving the implant were more likely to maintain opioid abstinence than those receiving sublingual buprenorphine.[1]

While the treatment has the potential to provide important benefits to patients, its price places it out of reach of many of those in need. Drugs.com lists a price of $5,175.80 for the 6 month supply, creating a yearly price per patient of $10,351.60.[2] This figure does not include implantation costs.

The sole patent listed in the FDA Orange Book for Probuphine is 7,736,665, which provides exclusivity until 2024. The inventors were Rajesh Patel and Louis Bucalo, and the patent was assigned to Titan Pharmaceuticals. But the patent also disclosed the invention was conceived on a federal grant.

“STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
This invention was made in part during work supported by a grant from the National Institute of Mental Health (1R43 MH60037-01). The government has certain rights in the invention.”

Under the Bayh-Dole Act. and specifically 35 U.S.C. § 202(c)(4), the funding Federal agency retains “a nontransferable, irrevocable, paid-up license… to practice the invention or have the invention practiced throughout the world by or on behalf of the Government of the United States.” The royalty-free right can be used by the government or on its behalf at any time, without payment of royalty.

As the invention was partially or fully federally funded, the United States Government also retains “march-in” rights under 35 U.S.C. § 203, which allows the government to force the rights holder of a federally-funded invention “to grant a nonexclusive, partially exclusive, or exclusive license in any field of use to a responsible applicant or applicants, upon terms that are reasonable under the circumstances,” or, if the rights holder refuses, the government may itself grant the license. Utilizing these march-in rights requires a determination that at least one of four conditions (section 203(a)(1-4)) are met, but most relevant to the amendment is the requirement for “practical application” of the invention, which is defined in 35 U.S.C. § 201(f) as making the benefits of the invention “available to the public on reasonable terms.”

In addition to its initial funding, the National Institute on Drug Abuse provided $7,586,848 in funding for Phase 3 clinical trials for the medication. While Probuphine is protected by test data exclusivity until May 26th, 2019, the government may have rights to the test data. KEI has requested copies of any cooperative research and development agreements and copies of the grants related to this funding.

The United States is in the grip of an opioid addiction epidemic. Kaiser Family Foundation has found that only 40 percent of adults with opioid addiction have private insurance, while 30 percent rely upon Medicaid and 20 percent are uninsured.[3] For many of those suffering from addiction, the costs of this medication must be borne out of pocket.

This is a medication which has been proven to be effective. The government can use its existing rights to expand access and affordability. Earlier this month, President Donald Trump said that he would declare the opioid crisis a national emergency, and the President’s Commission on the opioid crisis recommended expanding access to medication assisted treatment in its report.[4] Action on expanding access to Probuphine is one important tool which the government already has at its disposal.


1 http://jamanetwork.com/journals/jama/fullarticle/2533504#Discussion

2 https://www.drugs.com/price-guide/probuphine

3 http://www.kff.org/uninsured/fact-sheet/6-things-to-know-about-uninsured-adults-with-opioid-addiction/

4 https://www.whitehouse.gov/sites/whitehouse.gov/files/ondcp/commission-interim-report.pdf

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