IP Law Daily Mylan escapes infringement liability for pursuing bivalirudin generic
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Thursday, April 6, 2017

Mylan escapes infringement liability for pursuing bivalirudin generic

By Mark Engstrom, J.D.

Mylan Inc. did not infringe two patents on pharmaceutical formulations of the anticoagulant drug bivalirudin, the U.S. Court of Appeals for the Federal Circuit has ruled. Because both patents included a pH-adjusted "batches" limitation that required a compounding process for "consistently" minimizing batch impurities through "efficient mixing"—a process that was described and defined in "Example 5" of the patent specifications—and because Mylan did not use the multiple mixing devices that were required by Example 5, the Federal Circuit reversed the judgment of infringement for one patent and affirmed the judgment of non-infringement for the other (The Medicines Company v. Mylan, Inc., April 6, 2017, Dyk, T.).

Lawsuit. In response to an Abbreviated New Drug Application (ANDA) by Mylan, which sought to market a generic version of the branded drug ANGIOMAX, The Medicines Company sued Mylan for the infringement of eight claims of U.S. Patent No. 7,582,727 and eight claims of U.S. Patent No. 7,598,343. Both patents pertained to pharmaceutical formulations or "batches" of bivalirudin, a synthetic peptide that prevents the clotting of blood during cardiac catheterization. The asserted claims were directed to the minimization of impurities in batches that were compounded with a base (to reduce acidity).

The district court held on summary judgment that Mylan’s ANDA did not infringe the asserted claims of the ’343 patent because Mylan’s generic did not satisfy the "efficient mixing" limitation of those claims. After a bench trial, the court held that the asserted claims of the ’727 patent were infringed because those claims did not include an "efficient mixing" limitation. Mylan appealed the district court’s judgment of infringement with respect to the ’727 patent, and Medicines cross-appealed the court’s summary judgment of non-infringement with respect to the ’343 patent.

Construction of "batches" limitation. Mylan successfully argued that the district court had erred by declining to interpret the claims of the ’727 patent to require "efficient mixing" as part of its "batches" limitation. According to the court, the batches limitation for both patents required "efficient mixing."

The court noted that the batches limitation restricted the claims of the ’727 patent (and the ’343 patent, as well) to batches that had a "maximum impurity level of Asp9-bivalirudin" that did not exceed "about" 0.6 percent. Properly construed, the batches limitation required the use of a process that achieved "batch consistency"—i.e., consistency between batches that were produced from the "same compounding process".

Medicines argued that the batches limitation was satisfied whenever an accused infringer consistently produced batches with Asp9 levels below 0.6 percent, and further argued that the claims did not require the use of a particular process to achieve batch consistency.

The court disagreed. First, adopting Medicines’ interpretation of the batches limitation would yield an unworkable claim construction because proof of infringement under that interpretation would necessitate forward-looking assessments of whether an accused infringer’s production of future or "potential" batches would likely generate Asp9 levels that were greater than about 0.6 percent.

Second, Medicines’ interpretation failed to consider the specification and prosecution history of the patents in suit, both of which showed that the disclosed invention was a compounding process that achieved batch consistency.

Finally, any remaining doubt that the batches limitation required a compounding process was dispelled by an admission by Medicines that, "[w]hen viewed in the context of the specification, it is readily apparent that the [definition of ‘pharmaceutical batches’] refers to the compounding processes described in the patents-in-suit".

Compounding process. The court had to decide what the "compounding process" entailed. Based on the intrinsic evidence of the patents in suit, the court concluded that the compounding process had to use "efficient mixing." Significantly, the patent specifications unequivocally stated that: (1) the "pH-adjusting solution will be efficiently mixed" and (2) the "[e]fficient mixing of the pH-adjusting solution ... will minimize levels of Asp9-bivalirudin." Moreover, apart from efficient mixing, no part of the patents’ disclosure taught another method that was capable of producing consistent batches.

Medicines argued that reading the batches limitation to require "efficient mixing" would render the asserted claims of the ’343 patent—which already recited an "efficiently mixing" step—superfluous. It further argued that the batches limitation extended to compounding processes that did not use efficient mixing. The court disagreed.

The recitation of other product-by-process limitations in the claims of the ’343 patent—"dissolving bivalirudin in a solvent to form a first solution" and "removing the solvent and pH-adjusting solution solvent"—meant that the claims of the patents in suit would merely overlap, and overlapping patent claims were not unusual.

For all of those reasons, the reading of the batches limitation that most naturally aligned with the patent’s description of the invention was one that required "efficient mixing," according to the court. To attribute to the claims a meaning that was broader than the meaning indicated in the patents and their prosecution history would "ignore the totality of the facts of the case and exalt slogans over real meaning," the court explained.

Meaning of "efficient mixing." Medicines argued that the common specification of the patents in suit defined "efficient mixing" as a mixing that was "characterized by minimizing levels of Asp9-bivalirudin in the compounding solution" (i.e., below 0.6 percent Asp9-bivalirudin in the intermediate solution). According to Medicines, that definition was controlling.

The court disagreed. Medicines’ characterization of "efficient mixing" was taken verbatim from the specification, but it did not purport to be definitional because it did not accord with the "linguistic formula" that the patentee had used to signal the designation of other defined terms, including "batches." More importantly, the construction was problematic because it amounted to a mere recitation of the results that were obtained from "efficient mixing," rather than a definition of what the efficient mixing process actually was.

In the court’s view, the phrase "efficient mixing" had to be defined in terms of the particular process or processes that were identified in the specifications, and only "Example 5" provided a clear delineation of those processes. Example 5 described "efficient mixing," in part and in general, as the addition of a pH-adjusting solution at a constant rate. The court concluded that a person of ordinary skill in the art would rely on the specifics of that Example to ascertain the metes and bounds of "efficiently mixing." Because Example 5 was the only embodiment of efficient mixing, it was "highly indicative" of the scope of the claims. The court thus construed "efficient mixing" to mean the efficient mixing conditions of Example 5.

Application to Mylan’s ANDA. The net effect of the Federal Circuit’s claim construction was that, to infringe either patent, the infringing batches had to be compounded using a process that employed the "efficient mixing" conditions of Example 5. Under that claim construction, Mylan’s ANDA did not infringe the asserted claims because Mylan did not use multiple mixing devices, as required by Example 5. The district court’s judgment was therefore reversed in part and affirmed in part.

The case is Nos. 2015-1113, 2015-1151, and 2015-1181.

Attorneys: Porter F. Fleming (Haug Partners LLP) for The Medicines Company. Shannon Bloodworth (Perkins Coie, LLP) for Mylan, Inc.; Mylan Pharmaceuticals Inc.; and Bioniche Pharma USA, LLC.

Companies: The Medicines Company; Mylan, Inc.; Mylan Pharmaceuticals, Inc.; Bioniche Pharma USA, LLC

MainStory: TopStory Patent FedCirNews

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