Amgen’s claims against Apotex’s Neulasta® (pegfilgrastim) and Neupogen® (filgrastim) biosimilars have failed at the district court level.  On September 6, 2016, the District Court for the Southern District of Florida found no infringement by Apotex of the only remaining patent in suit, U.S. Patent 8,952,138 (directed to protein folding).

Amgen initiated the litigation in August 2015, after the parties engaged in the “patent dance” provisions of the Biologics Price Competition and Innovation Act (BPCIA). Amgen accused Apotex’s biosimilar pegfilgrastim product of infringing U.S. Patent Nos. 8,952,138 and 5,824,784 under 271(e)(2)(C), and sought declaratory judgment of infringement under 102(a) and (g) for any commercial manufacture, use, sale, offer for sale, or importation of that product.  A subsequent consolidated suit filed several months later alleged infringement of the ‘138 patent and U.S. Patent No. 6,162,427 with respect to Apotex’s biosimilar filgrastim product.  All claims and counterclaims with respect to the ’784 and ’427 patents were subsequently dismissed by stipulation, leaving only the ’138 patent at issue.

Amgen also alleged that Apotex’s pre-licensure notice of commercial marketing was ineffective. Amgen sought a preliminary injunction requiring Apotex to provide 180 days of notice before commercial marketing if and when the FDA licensed the biosimilars. The court granted Amgen’s motion for a preliminary injunction, which was affirmed by the Federal Circuit on appeal.

Following a bench trial held the week of July 11, 2016, the district court granted Amgen’s motion pursuant to Fed. R. Civ. P. 52 for judgment on partial findings that the asserted claims of the ’138 patent were not invalid on grounds of anticipation, obviousness, written description, and indefiniteness.  The district court reserved judgment on Apotex’s enablement defense and entertained post-trial briefing with respect to Apotex’s motion for judgment of non-infringement.

This week, the court ruled that Apotex’s biosimilar pegfilgrastim and filgrastim products, which have yet to be approved by the FDA, do not infringe the ’138 patent literally or under the doctrine of equivalents.  In particular, Amgen failed to prove by a preponderance of evidence that Apotex’s protein refolding process met two claim limitations: (1) a “high protein concentration” at or above about 1 g/L and (2) a redox component having a redox buffer strength of 2 to 100 mM.  At the same time, Apotex demonstrated its process did not infringe the claims because its protein concentration was outside of the claimed range and its process uses a smaller volume of a more concentrated redox component than is claimed in the ‘138 patent.  Finding that “a judgment of Apotex’s non-infringement firmly and clearly resolves this case,” the court declined to reach Apotex’s enablement defense.  The court also declined to award attorneys’ fees, given that Amgen’s actions in asserting its patent rights were “reasonable.” However, the court entered a permanent injunction, consistent with the earlier preliminary injunction affirmed by the Federal Circuit, requiring Apotex to provide Amgen with at least 180 days’ notice before the date of the first commercial marketing, if the FDA approves Apotex’s biosimilars.  Having resolved all outstanding issues, the court directed the clerk to close the case and deny as moot any other pending motion.

The parties have 30 days from entry of final judgment to appeal the validity and non-infringement rulings.  As we reported previously, in August 2016, Apotex filed a petition seeking inter partes review (IPR) of all claims of the ’138 patent. Apotex’s IPR petition is still pending before the PTO, and Amgen has until early November 2016 to file a preliminary response.  If the PTAB decides to proceed with a trial, the IPR can proceed in parallel with any appeal of the district court judgment.  This could provide Apotex with another opportunity to invalidate the ’138 patent.

If and when approved, Amgen’s pegfilgrastim product would be the first Neulasta® biosimilar on the market, and its filgrastim product would be the second Neupogen® biosimilar product to enter the market.  Sandoz launched its filgrastim biosimilar, ZARXIO®, on September 15, 2015.

We will continue to monitor this litigation and provide updates.