January 23, 2017
Case Name: Mylan Institutional LLC v. Aurobindo Phama Ltd, 2:16-cv-00491-RWS-RSP, 2016 U.S. Dist. LEXIS 180551 (E.D. Tex. Nov. 21, 2016) (Payne, MJ)
Drug Product and Patents-in-Suit: isosulfan blue; U.S. Patents Nos. 7,662,992 (“the ’992 patent”), 8,969,616 (“the ’616 patent”), and 9,353,050 (“the ’050 patent”)
Nature of the Case and Issue(s) Presented: Plaintiffs Mylan and Apricore (“Apricore”) make a highly pure isosulfan blue compound. Isosulfan blue is a dye used to map the lymphatic system surrounding a tumor site prior to a biopsy and had been used by doctors since the 1960s. Apricore’s isosulfan blue formulation improved on existing isosulfan blue formulation by reaching an unprecedented 99% purity. The patents-in-suit claimed the high purity compound as well as the process for manufacturing it.
Aurobindo filed an ANDA seeking to market its own generic isosulfan blue formulation. Aurobindo’s isosulfan blue was identical to Apricore’s, except that it included manganese dioxide instead of silver oxide. After the FDA approved Aurobindo’s ANDA, Apricore sued for patent infringement and moved for a preliminary injunction to prevent the import of Aurobindo’s formulation into the US. The court found that Apricore was likely to succeed on the merits and would be irreparably harmed if Aurobindo’s infringement were to continue, and granted Apricore’s motion for a preliminary injunction.
Why Apricore Prevailed: The court first addressed the process patents. The parties’ processes for formulating their respective isosulfan blue products were identical, except Aurobindo used manganese dioxide and Apricore used silver oxide. Thus, the only issue was whether manganese dioxide was equivalent to silver oxide. Both compounds performed the same function: converting isoleuco acid to isosulfan blue acid. Additionally, the patent specification disclosed a preferred range of isosulfan blue acid yield resulting from the claimed process. Both silver oxide and manganese dioxide produced yields within this range and thus were functionally equivalent.
Next, the court evaluated the product patent. Here, the dispute centered on the claimed term “purity.” Aurobindo argued that purity referred to the absence of extraneous material in the formulation. Apricore, on the other hand, advocated for a more traditional definition of “purity”—the absence of reaction by-products. Apricore’s construction was supported by numerous extrinsic publications and was not contradicted by anything in the patent. Further, Apricore’s construction was consistent with prior Federal Circuit constructions of that term. Thus, the court adopted Apricore’s construction and, under that construction, Aurobindo’s product infringed.
Addressing Aurobindo’s invalidity arguments, the court found that it was equally unlikely to succeed on the merits. Aurobindo submitted documents from Sigma-Aldrich, a biochemical company, indicating that the company made and sold isosulfan blue with a purity greater than 99%. Those documents, however, did not necessarily refer to isosulfan blue, but rather a broader range of dyes known as Patent Blue Violet dyes. Further, additional documents from Sigma-Aldrich indicated that the record indicating a greater than 99% purity dye was erroneous. The court therefore determined that the Sigma-Aldrich documents were unlikely to invalidate the patents-in-suit. Aurobindo also submitted publications indicating that high purity dyes could be made with silver oxide as a reagent. But the court found no motivation to combine those publications because those dyes were used as chemical-weapon detectors, not pharmaceutical dyes.
Similarly, the court ruled that Aurobindo was unlikely to succeed in invalidating the product patent, finding Aurobindo’s prior-art references lacking. The court reasoned that Apricore did not just claim purifying existing isosulfan blue using known methods. Instead, as discussed above, the process of creating high purity isosulfan blue was its own patentable invention. Thus, one of ordinary skill would not have combined the Aurobindo’s prior art, and the product was not obvious.
Finally, the court concluded that Apricore would be irreparably harmed if it were not to obtain a preliminary injunction. More than half of Apricore’s revenue resulted from sales of its isosulfan blue product. The introduction of Aurobindo’s product to the market would cause significant price erosion, forcing Apricore to abandon development of new products. Absent infringement, Aurobindo would not be able to make its competing product. Further, the court reasoned that it was in the public’s interest to protect valid pharmaceutical patents, to encourage companies to disclose the formulation of their products.