In two final written decisions (IPR2015-01093 and IPR2015-00990), the PTAB found that challenged claims in Shire’s U.S. Patent No. 7,056,886 (the ’886 patent) were invalid as obvious. The decisions highlight potential issues related to patents directed to pharmaceutical formulations that petitioners and patent owners alike may want to consider if confronted with an IPR related to such subject matter.

The Coalition for Affordable Drugs filed two petitions for IPR, one challenging claims 1−45 of U.S. Patent No. 7,056,886 (IPR2015-01093) and one challenging claims 46−52 and 61−75 of the ’886 patent (IPR2015-00990).

In IPR2015-01093, the PTAB instituted a review of claims 1-27, 31-40, and 44-45 based on various combinations of references under 35 U.S.C. § 103(a), and in IPR2015-00990, the PTAB instituted a review of claims 46-52 and 61-75 based on various combinations of references under 35 U.S.C. § 103(a).

The ’866 patent is directed to a glucagon-like peptide 2 (GLP-2) formulation comprising (a) a GLP-2 or an analog thereof, (b) a phosphate buffer, (c) L-histidine, and (d) mannitol or sucrose (as a bulking agent). As stated in the ’866 patent, the “invention is directed to formulations of GLP-2 peptides and analogs thereof exhibiting superior stability following storage and/or exposure to elevated temperatures.”

The Petitioner argued that the cited prior art provided relevant guidance for preparing storage stable lyophilized formulations for peptide formulations, and that “[t]he claimed GLP-2 formulation is nothing more than a combination of known ingredients for a predictable result of stability as confirmed by routine testing.” The Petitioner relied on various main references, which were cited as disclosing the following: (1) lyophilized GLP-2 and GLP-2 analog formulations (Drucker ’379; Drucker ’547; and Drucker ’600); (2) histidine and sugars (such as sucrose) may be used to stabilize lyophilized peptide formulations (Osterberg); (3) histidine and conventional bulking agents or excipients (such as lactose and mannitol) are useful to stabilize glucagon formulations (Kornfelt).

The Patent Owner argued that a person of skill in the art would not have had a reasonable expectation of success in combining the references because Kornfelt discloses the stabilization of glucagon (which the Patent Owner argued is not predictive of stabilization of GLP-2) and that glucagon and GLP-2 have vastly different physical characteristics that affect aggregation rate and stability. The Patent Owner further argued there would be no reasonable expectation of success in combining the references because histidine is a “problematic excipient.” Finally, the Patent Owner argued that the “protein/peptide stabilization is far from routine or predictable.”

In its analysis, the PTAB stated that “[t]he question before us is whether a person of ordinary skill in the art would have been motivated to formulate GLP-2 analogs with histidine and the bulking agent/excipient mannitol with a reasonable expectation of success,” and determined “that Petitioner has established that a person of ordinary skill in the art would have been motivated and guided by the teachings of Osterberg and Kornfelt to modify the lyophilized GLP-2 analog formulation disclosed in either Drucker ’379 or Drucker ’574 [or ’600].”

The PTAB acknowledged “the numerous differences between a GLP-2 analog and glucagon highlighted by Patent Owner,” but were not persuaded that a person of ordinary skill in the art would not have had a reasonable expectation of success in using histidine in GLP-2 formulations based on these differences. The PTAB pointed out that “Osterberg discloses that the addition of amino acids and sugars function to stabilize protein formulations generally, and Patent Owner has not directed us to sufficient evidence to support a conclusion that a person of ordinary skill in the art would have expected difficulty in formulating a GLP-2 analog by following the parameters disclosed in Osterberg.”

The PTAB concluded that development of the claimed formulation was merely routine experimentation:

That the inventors of the ’866 patent discovered that a particular GLP-2 analog performs best with a certain combination of amino acid and sugar, namely histidine and mannitol, does not persuade us by itself that the subject matter of the claims of the ’866 patent is nonobvious. The preponderance of evidence of record shows that the identification of the optimal sugar and amino acid to add to a formulation for stability purposes was nothing more than routine experimentation.

The Patent Owner also argued that secondary considerations of unexpected results, commercial success, and the satisfaction of a long-felt need supported nonobvious of the challenged claims. The PTAB considered each of the secondary considerations, but did not find them persuasive. With respect to the proffered unexpected results, the PTAB noted that results were expected based on the disclosures in the prior art. As to commercial success, the PTAB stated the Patent Owner’s analysis was flawed, because the Patent Owner did not establish a nexus between the sales of Gattex® (the covered product) and the claims of the ’886 patent in view of other patents listed in the Orange Book. Finally, with respect to the Patent Owner’s evidence of long-felt need for its marketed product Gattex®, the PTAB stated that “Patent Owner does not provide sufficient evidence to permit a determination as to whether the long-felt need was met by the discovery of GLP-2 analogs having the necessary activity (disclosed in the prior art), or the use of L-histidine and mannitol or sucrose in a stabilized GLP-2 analog formulation.”

Therefore, the PTAB concluded that the challenged claims were obvious. In doing so, the PTAB highlighted many issues surrounding formulation patents that petitioners and patent owners should consider in post-grant proceedings related to formulation patents, including the importance of tailoring secondary considerations to the formulation patent itself.