Most of our readers are familiar with ClinicalTrials.gov. It is a registry of clinical trials maintained by the National Library of Medicine. By law, any sponsor of a clinical trial to be performed in the United States or under the auspices of an Investigational New Drug Application must publish the details of its trial on this web site before it has commenced the trial. Many other countries maintain similarregistries.
In Ex parte John Simard, 2017 Pat. App. LEXIS 9241 (P.T.A.B. Sept. 5, 2017), the question was whether the publication of a clinical protocol on ClinicalTrials.gov anticipated the underlying method of treatment, when the clinical trial had not actually been performed. The Board had little problem answering this question. According to the Board,
“Anticipation does not require actual performance of suggestions in a disclosure. Rather, anticipation only requires that those suggestions be enabling to one of skill in the art."
The Appellant argued that claim 1 was not anticipated because it required that "the chance of a major adverse clinical event [be] reduced." The Board had little difficulty with this argument either because, under well-worn principles of inherency, a method of treatment will be anticipated where the intended result is inevitable. According to the Board:
“administering an anti-IL-1α antibody would inevitably lead to a reduction in the chance of a MACE or the development of restenosis.”
The more interesting question, which the Board did not address, is whether a publication on ClinicalTrials.gov will render a claimed method of treatment obvious when the publication does not describe every element of the claim. In this case, for example, ClinicalTrials.gov allegedly did not describe the dose of the medication, or the duration of treatment needed for a therapeutic effect. The applicant potentially could have overcome the anticipation rejection simply by incorporating these elements into the claim.
The Examiner could have rejected this revised claim for obviousness, but this would have imposed an additional burden on the Examiner. In particular, the Examiner would have had to establish a reasonable expectation of success that the method underlying the protocol would actually succeed.
A decision by the Board in a 2015 inter-parties review gives some insight into the meaning of “reasonable expectation of success” in this context. See Coalition for Affordable Drugs V LLC (CFAD) against Biogen MA Inc. IPR2015-01136, Paper 23 (Sept. 2, 2015). There, the Board rejected an obviousness challenge to a method of treating multiple sclerosis, even though a phase II trial for the treatment had been published on ClinicalTrials.gov, because ClinicalTrials.gov, at best, describes a “possible therapeutic efficacy in MS.” According to the Board, ClinicalTrials.gov
“might support a finding that one skilled in the art “hopes” DMF will be useful in treating MS. However, … a ‘hope’ may or may not come to pass.”
Because a reader of the clinical trial in Coalition for Affordable Drugs would not “reasonably expect” the trial to succeed, the method underlying the trial was not obvious.
The differences in results between these two cases could lead one to conclude that the publication of a protocol on ClinicalTrials.gov can anticipate the underlying method of treatment, but not render the method of treatment obvious, but we would caution against such an expansive reading of these cases. The Coalition for Affordable Drugs case, after all, involved a phase II clinical trial, where efficacy was still being investigated. Moreover, section 2173 of the MPEP instructs Examiners that,
“as a general rule, if an applicant has initiated human clinical trials for a therapeutic product or process, Office personnel should presume that the applicant has established that the subject matter of that trial is reasonably predictive of having the asserted therapeutic utility.”
Resolving a “reasonable expectation of success” question probably requires a much more intensive factual investigation. The simplest solution to this quandary, under U.S. practice, may be to file the patent application before the publication on ClinicalTrials.gov. Such an application would be prophetic, without actual clinical data, but MPEP 2173 essentially commands Examiners to accept that the application is enabled. A more difficult question is whether other examining authorities, such as the Chinese Patent Office, will accept a prophetic application, and what data might be used to satisfy these other examining authorities.
As this discussion makes clear, publications on clinical trial registries present vexing issues for the patent attorney, that require careful analysis and good legal judgment.