Shire Orphan Therapies LLC v. Fresenius Kabi USA, LLC

Case Name: Shire Orphan Therapies LLC v. Fresenius Kabi USA, LLC, Civ. No. 15-1102-GMS, 2018 U.S. Dist. LEXIS 93911 (D. Del. June 5, 2018) (Sleet, J.) 

Drug Product and Patent(s)-in-Suit: Firazyr® (icatibant acetate); U.S. Patent No. 5,648,333 (“the ’333 patent”) 

Nature of Case and Issue(s) Presented: At issue was a peptide patent directed to icatibant acetate, which is administered in a single-use, prefilled syringe for subcutaneous administration to treat acute attacks of hereditary angioedema. Fresenius argued that the ’333 patent was invalid for double patenting and unenforceable under the doctrine of prosecution laches. Judge Sleet disagreed.

Why Shire Prevailed: With regard to double patenting, the court found several differences between the prior-art peptide and the peptide claimed in the ’333 patent. Specifically, Judge Sleet stated that his analysis hinged on whether: (i) the removal of the N-terminus modification Fmoc from the peptide of the prior-art patent resulted in the claimed molecule; and (ii) whether the N-terminus modifications in the prior art peptide were intended to be permanent and integral components of the final peptide. Judge Sleet answered both questions in the negative and further explained that a POSA would not have been motivated to make the corresponding changes between the prior-art peptide and that claimed in the ’333 patent.

The court also found evidence of long-felt need because Firazyr could be self-administered, without requiring intervention by a healthcare professional, whereas the prior-art injections could be administered only in a hospital setting by IV. Moreover, the court found that Fresenius failed to establish that Firazyr was prescribed for reasons other than its safety, efficacy, and convenience, thereby indicating that it was a commercial success. Finally, the court noted that Fresenius’ alleged evidence of contemporaneous development was unpersuasive since it post-dated the first publication of the patented invention. On balance, the court determined that Fresenius failed to prove that the ’333 patent was invalid for double patenting.   

With regard to prosecution laches, Fresenius argued that plaintiffs unreasonably delayed prosecution of the ’333 patent by failing to provide a substantive PTO response between 1991 and 1995. Specifically, Fresenius argued that plaintiffs failed to provide the PTO with in vivo data to support the utility of the alleged intention, instead arguing that the proffered in vitro data were sufficient. Fresenius further argued that plaintiffs were in possession of the in vivo data relating to icatibant as early as March 1989. The court noted, however, that at the time of prosecution, the M.P.E.P. permitted utility to be “established by clinical or in vivo or in vitro data, or combinations.” The court further noted that filing the application underlying the ’333 patent on June 6, 1995—the day before the Uruguay Round of the General Agreement on Tariffs and Trade went into effect—was immaterial because the patentee’s desire to maximize its patent term was neither unreasonable nor unexplained. Finally, the court explained that Fresenius could not demonstrate prejudice because it did not invest in, work on, or use icatibant during the alleged four-year period of delay—it did not begin its icatibant project until 2014.