The U.S. Court of Appeals for the Federal Circuit recently issued a non-precedential Rule 36 affirmance of the Patent Trial and Appeal Board (PTAB) in In re Adhami, No. 2024-1218, 2025 WL 1949797 (Fed. Cir. July 16, 2025).[1] This appeal concerned the question of when and how a single-patient study can provide sufficient data to provide an enabling disclosure to support patent claims.
N=1 clinical trials are a common phenomenon. The U.S. Food and Drug Administration will frequently grant “compassionate use” dispensations to individual patients whose illness is so severe that they are willing to try an experimental drug. Because these dispensations are granted on a case-by-case basis, the patient population enrolled in such compassionate use studies is necessarily small—typically a single patient. Where an encouraging, novel result emerges from such a trial, the investigator might naturally wonder whether this compassionate use result can be applied to other patients. If it seems likely that what worked for one patient might work for another, then the next logical question to ask is whether this novel and interesting new treatment is patentable.
Dr. Eftim Adhami asked the same question after he observed a curious incident in which a 27-year-old male arrived at an emergency room where Dr. Adhami worked. The patient was in coma with a blood ethanol concentration of 700 mg/dL. Not much was known about the unconscious patient at the time, but when he emerged from his coma 10 days later, friends showed up and explained that the patient did not typically drink alcohol—so, he did not have tolerance to alcohol—but that he had drunk a lot on the day of his hospital admission during a drinking competition in a party.
Meanwhile, hospital records showed that he was HIV+. Blood tests showed an HIV viral load of 60,000 vg/mL at the time. He did not have any more records until this admission and he never took antiretroviral therapy.
During the ICU stay, he was maintained in coma with propofol infusions, opioids, and muscle paralyzers. Fluids were administered intravenously, mostly as Ringer’s lactate and dextrose 5% in water. To avoid precipitous alcohol withdrawal, the patient was treated with ethanol infusion to decrease the concentration slowly over days. The day after admission, his blood alcohol concentration was 300 mg/dL.
The patient recovered uneventfully after 10 days, after which he was extubated. The patient saw an internist at the same hospital two years later and records of that encounter showed normal blood tests, including absolute CD4+ numbers. More remarkably, his HIV viral load at this time was undetectable—despite the fact that the patient had never started any antiretroviral medication.
Based on this singular incident, Dr. Adhami filed a patent application (U.S. Publication No. 2017/0281676) claiming a novel method for treating HIV using a combination of anesthesia and the administration of certain chemicals, including ethanol, isopropyl alcohol, methanol, and ethylene glycol. The method involved placing the patient under general anesthesia and administering these chemicals to achieve a therapeutic effect. The application explained Dr. Adhami’s theory that the alcohol (or other disinfectant) kills the virus, while the anesthesia and other chemicals slow metabolism enough to prevent off-target damage to the patient’s own organs. The claims were rejected by the Examiner on the grounds of failing to meet the enablement and written description requirements.
The legal issues in this case revolved around whether the patent application met the requirements of enablement and written description under 35 U.S.C. § 112(a). The Examiner argued that the specification did not adequately describe how the claimed method could achieve the intended therapeutic effect, nor did it provide sufficient guidance for a person skilled in the art to practice the invention without undue experimentation.
The PTAB reversed the written description rejection, but affirmed the enablement rejection. The PTAB found that the application did not satisfy the enablement requirement because it lacked sufficient evidence to demonstrate that the claimed method could effectively treat HIV in humans. In particular, the PTAB noted that the “Specification proposes that treatment with ethanol reduces the viral load in a patient to zero (‘to provide a permanent destruction of HIV or other viruses with a single treatment procedure’ (Spec. ¶ 11)).” This meant that the application needed data to make plausible not merely that the claimed invention should improve viral load, but that it could reliably eliminate the virus entirely, and in a human body—not just a test tube.
The PTAB also noted that the specification provided only the anecdotal example of the single, 27-year-old patient, without considering other factors that could have contributed to this outcome. Moreover, the PTAB highlighted the unpredictability of using the claimed chemicals for treating HIV, and cited several existing studies in which alcohol consumption increased HIV viral loads.
This is not to say that enablement cannot be acknowledged based on an N=1 case study (see, e.g., U.S. Application No. 12/744,131). One can take away several practice points from Adhami that one should consider when pursuing an invention discovered in this sort of N=1 study:
- The title of Adhami’s application was “HIV-Cure,” which sets a high bar for the amount of proof necessary to establish enablement across the entire scope of the claims. It is important not to “oversell” the utility that the invention is disclosed as providing.
- There were known reports in the published literature that alcohol exacerbates HIV infection, so Adhami’s claims were running counter to the weight of evidence. That makes a plausible basis to argue non-obviousness, but it also means that the argument for enablement needs to be able to speak to these known facts in the literature. An inventor pursuing an invention based on an N=1 study would do well to search the literature for such counter-examples before filing, and include explanations to account for these counter-examples in the application.
- Finally, Dr. Adhami provided an expert declaration averring that the claims “relied on ‘reputable studies and medical journals with an ample amount of laboratory and human data’,” but the PTAB noted that no studies, journals, or data were specifically named or provided in the declaration. When providing a declaration to supplement the evidentiary record, it pays to be specific about the sources of the data and the names of the expert, in order for the fact-finder to be able to accord credible weight to the assertions in the declaration.
[1] Appeal from Ex parte Adhami, Appeal 2023-002654, 2023 WL 4842063 (Patent Tr. & App. Bd.).
