Petitioners Must Present Sufficient Evidence to Establish Inherency
Last Friday the Patent Trial and Appeal Board (PTAB) denied four Sandoz Inc. petitions for instituting inter partes review (IPR) of U.S. 8,455,524 (IPR2015-00005), U.S. 7,612,102 (IPR2015-00006), U.S. 7,659,290 (IPR2015-00007), and U.S. 7,659,291 B2 (IPR2015-00008) (referred to herein as the “EKR Patents”). The EKR Patents are assigned to EKR Therapeutics, a wholly owned subsidiary of Chiesi USA, Inc. The PTAB concluded that the “Petitioner has not established a reasonable likelihood that it would prevail in showing the unpatentability of at least one challenged claim.” See, e.g., IPR2015-00005 at 2. The PTAB reached this conclusion based, in part, on Sandoz’s failure to “present sufficient evidence” in support of its arguments that the challenged claim elements in the four patents were inherent.
The EKR Patents relate to ready-to-use injectable formulations of nicardipine or its pharmaceutically acceptable salt (e.g., nicardipine hydrochloride) for the treatment of cardiovascular and cerebrovascular disorders. The claimed formulations, when stored in a container for some period of time (e.g., at least 3 months) at room temperature exhibit less than a 10% decrease in the concentration of nicardipine or its salt, and a total impurity formation of less than about 3%. See, e.g., claim 1 of the ‘291 patent, and claim 1 of the ‘524 patent. The claims in all four patents share two common elements: i) stability (“exhibit less than 10% decrease in the concentration”) and ii) total impurity (“total impurity formation of less than about 3%”) of nicardipine or its pharmaceutically acceptable salt formulations, and also require a concentration of “about 0.1 to 0.4 mg/mL” nicardipine or its salt concentration in the formulation. See, e.g., IPR2015-00008 at 5 (“[e]ach challenged claim recites a method of using a nicardipine hydrochloride formulation having a concentration of between 0.1 to 0.4 mg/mL and recites certain threshold stability and impurity requirements.”).
In its petitions, Sandoz alleged that the claims in the EKR Patents are unpatentable as obvious under 35 U.S.C. § 103 because the two elements (stability and impurity) are inherent properties in view of the combined teachings in four prior art references. Arguing that the nicardipine hydrochloride formulations are inherently stable in a specified container, Sandoz argued that a person of ordinary skill in the art would have expected “less than 10% decrease in the concentration” in a “pharmaceutically acceptable container” because one reference (McFarlane, U.S. Patent 5,164,405) “discloses 1 mg/mL and 2.5 mg/mL nicardipine hydrochloride solutions decrease less than 10% after 12 months at room temperature,” and a second reference (JP 2002-177364) “expressly teaches that the specified container is designed to achieve ‘minimal reduction in the potency of a drug . . . .’”. See, e.g., IPR2015-00007 at 8-9. In challenging the total impurity (“total impurity formation of less than about 3%”) limitations in the claims, Sandoz further argued that the “total impurity formation over time is an inherent property of nicardipine hydrochloride solution and the container within which it is stored.” See, e.g., IPR2015-00005. Sandoz supported its positions with “an analysis and detailed claim chart mapping each element of the claims to a teaching in the combined prior art,” (see, e.g., IPR2015-00008 at 6), as well as an expert declaration.
The PTAB was not persuaded by Sandoz’s arguments. Relying on the Federal Circuit’s guidance on using the inherency doctrine in the context of obviousness (Bettcher Indus., Inc. v. Bunzl USA, Inc., 661 F. 3d 69, 639 (Fed. Cir. 2011)), the PTAB advised that “Petitioner must present sufficient evidence, either from the prior art or through its own testing data, to show that nicardipine hydrochloride solutions prepared as suggested in the prior art, in fact, would satisfy the recited impurity-formation limitation, when stored in a container taught by JP ‘364.” E.g., IPR2015-00005 at 11. The PTAB found that in each of its petitions Sandoz did not present sufficient evidence, either from the prior art or through its own independent testing data, to show that, “when stored in a container . . . nicardipine hydrochloride solutions prepared . . . in fact, would be ‘stable at room temperature for 6 months or longer . . . .” IPR2015-00006 at 14.
In one denial, the PTAB noted that the stability data disclosed in McFarlane relates to nicardipine hydrochloride solution having concentrations of 1.0 mg/mL and 2.5 mg/mL, both value of which are outside the claimed concentration range of “between 0.1 to 0.4 mg/mL”. See, e.g., IPR2015-00005 at 12. Because Sandoz did not present evidence, e.g., independent testing data, to show that a formulation comprising the claimed 0.1 to 0.4 mg/mL of nicardipine hydrochloride would be stable when stored in a container at room temperature, the PTAB determined that Sandoz had not established the requirement to show that the stability was necessarily present, or the natural result of the combination of elements disclosed in the reference. See, e.g., IPR2015-00008 at 7; see also IPR2015-00006 at 14 (“Petitioner must present sufficient evidence…through its own testing data….”).
These four decisions serve collectively as a helpful reminder on the support required when relying on the doctrine of inherency, and demonstrate the PTAB’s view that petitioners should be rigorous when arguing inherency, and may even be required to present independent testing data as evidence that one or more claim elements are necessarily present or otherwise the natural result of the combination of elements disclosed. These decisions also provide patent owners an insight on how to counter obviousness challenges relying on the inherency doctrine.