Those who follow this blog know that we are strong proponents of “subset” patents. These patents will typically claim a subset of a group previously included in a clinical study, not specifically evaluated in the previous clinical study based on their defining characteristics. The subset often corresponds to the inclusion criteria of a subsequent clinical trial.
In GRÜNENTHAL GMBH, Petitioner, v. ANTECIP BIOVENTURES II LLC, Patent Owner, 2020 Pat. App. LEXIS 12114 (P.T.A.B. December 22, 2020), the PTAB invalidated a subset patent because the subset of patients claimed in the patent was sufficiently addressed in a previously published clinical study. The drug claimed was neridronic acid. Antecip’s patent, U.S. Patent No. 9,820,999 B2 (the ’999 patent), claimed the use of neridronic acid to treat complex regional pain syndrome (CRPS) triggered by a bone fracture. Specifically, claim 1 recited:
“1. A method of treating pain associated with complex regional pain syndrome (CRPS) comprising selecting a human being having CRPS triggered by bone fracture and administering neridronic acid or a pharmaceutically acceptable salt thereof to the human being, wherein the treatment is effective in reducing pain.”
The prior art included a study of neridronic study in CRPS (Varenna 2012), but the study was not limited to CRPS triggered by bone fracture. Only 11 of the 41 patients enrolled in the neridronic acid arm of the study had CRPS triggered by a bone fracture, and only 17 of the 41 patients enrolled in the placebo arm had CRPS triggered by a bone fracture. The inclusion criteria for the study did not include bone fracture, and the patients in the study were not stratified based on bone fracture.
Nevertheless, the PTAB agreed with Grünenthal that Varenna 2012 identified “a subset of patients in a human clinical study that experienced bone ‘fracture’ as a ‘precipitating event’” for CRPS, and that Varenna 2012 reported that, “in that subset of patients, the administration of neridronate effectively mitigated pain.” This disclosure, according to the PTAB, was sufficient to anticipate the claim. The PTAB specifically credited Grünenthal’s characterization of a multivariate analysis that Varenna 2012 performed which determined that no baseline variables affected the outcome. Specifically, the PTAB agreed with Grünenthal’s conclusion that this multivariate analysis disclosed that “the particular type of precipitating event did not influence outcomes in the study, indicating that patients with all types of precipitating events, including fractures, benefited from the neridronate treatment.”
The PTAB next turned to Antecip’s argument that Varenna 2012 did not disclose “selecting” a CRPS patient based on bone fracture as a triggering event, as required in claim 1 of the ‘999 patent. Antecip acknowledged that Varenna 2012 included such patients in the study, but argued that Varenna did not specifically select these patients for inclusion in the study. According to Antecip:
“Varenna 2012 does not disclose deliberately selecting humans suffering from CRPS because their CRPS was caused by bone fracture. ‘Selecting’ requires deliberation. It is not enough to simply apply the claimed method to people who happen to have CRPS that happens to have been caused by bone fracture; the selection must have been deliberately made based on those criteria. Varenna 2012 does not disclose ‘selecting’ in this way.”
The PTAB rejected Antecip’s argument for two reasons. First, from a definitional standpoint, the PTAB saw no distinction between the terms “including” and “selecting.” The PTAB stated:
“We see no meaningful distinction between including a patient in a study, which involves treating that patient with neridronate, and selecting a patient for treatment with neridronate. Thus, in our view, the 11 patients included in the neridronate arm of the study [that had a bone fracture as a precipitating event] were, in essence, selected for treatment with neridronate.”
The PTAB also rejected Antecip’s arguments based on the doctrine of inherency, and the Federal Circuit’s earlier decision in In re Montgomery, 677 F.3d 1375, 1381 (Fed. Cir. 2012). According to the PTAB,
“In addition, these facts are similar to Montgomery where the drug ramipril was administered to patients in need of stroke prevention and our reviewing court found that ‘efficacy is inherent in carrying out the claim steps.’”
In other words, it did not matter what was in the mind of the investigator when he or she included the patient in the study. The “manipulative” steps recited in the claims are all that mattered, and Varenna 2012 had clearly performed those steps, by treating patients with CRPS triggered by bone fracture.
