Earlier this month, Amgen initiated suit against Apotex in the Middle District of Florida, alleging infringement of U.S. Patent No. 9,856,287 (“the ’287 patent”). This is the third complaint that Amgen has brought against Apotex under the Biologics Price Competition and Innovation Act (the “BPCIA”), based on Apotex’s abbreviated biologic license applications (“aBLAs”) for biosimilars of Amgen’s cancer drugs Neupogen® (filgrastim) and Neulasta® (pegfilgrastim).[1]

As described in detail in our previous posts here and here, Amgen previously sued Apotex in the Southern District of California in August 2015 for infringing two patents, U.S. Patent Nos. 8,952,138 (“the ’138 patent”) and 5,824,784 (“the ’784 patent”), in connection with its biosimilar of Neulasta®, and then again in October 2015 for infringing the ’138 patent and U.S. Patent No. 6,162,427 (“the ’427 patent”), in connection with its biosimilar of Neupogen®. The two cases were consolidated in November 2015. Following the district court’s dismissal of all claims and counterclaims related to the ’427 and ’784 patents on June 14, 2016, the only remaining issue was with regard to the infringement of the ’138 patent, which was drawn to a method of refolding a protein. The district court ultimately found that Apotex did not infringe the ’138 patent, and on November 13, 2017, the Federal Circuit affirmed.

The ’287 patent issued earlier this year on January 2, 2018, and is also directed to methods of protein refolding in non-mammalian expression systems. Representative claim 16 of the ’287 patent recites:

16. A method of refolding proteins expressed in a non-mammalian expression system, the method comprising:
    preparing a solution comprising:
    the proteins;
    at least one ingredient selected from the group consisting of a denaturant, an aggregation suppressor and a protein stabilizer;
    an amount of oxidant; and
    an amount of reductant,
    wherein the amounts of the oxidant and the reductant are related through a thiol-pair ratio and a thiol-pair buffer strength,
    wherein the thiol-pair ratio is in the range of 0.001-100, and
    wherein the thiol-pair buffer strength maintains the solubility of the solution; and
    incubating the solution so that at least about 25% of the proteins are properly refolded.

Since the ’287 patent issued after Amgen provided Apotex with lists of patents which may be infringed for both aBLAs pursuant to 42 U.S.C. § 262(l)(3)(A), Amgen supplemented its lists pursuant to § 262(l)(7) to include the ’287 patent on January 31, 2018. The complaint alleges that on March 2, 2018, Apotex provided Amgen with its statements under 42 U.S.C. (l)(3)(B), explaining why the ’287 patent is invalid, unenforceable, and/or is not infringed based on its pegfilgrastim aBLA and the filgrastim aBLA. Amgen seeks to push off the launch of both of Apotex’s biosimilar products for another two decades, until the expiration of the ’287 patent.

[1] Apotex’s aBLA for filgrastim was accepted by the FDA for review on February 13, 2015; the aBLA for pegfilgrastim was accepted in December 2014.