Pfizer Inc. v. Mylan Pharms. Inc.

Case Name:  Pfizer Inc. v. Mylan Pharms. Inc., Civ. No. 10-528-GMS, 2014 U.S. Dist. LEXIS 150283 (D. Del. Oct. 22, 2014) (Sleet, J.) (When a POSA would have to undertake significant guesswork to vary the parameters of prior-art compounds in order to formulate the claimed composition, and prior-art lead compounds taught away from the claimed composition, the court found the patents-in-suit not obvious.) 

Drug Product and Patent(s)-in-Suit: Sutent® (sunitinib malate); U.S. Pats. Nos. 6,573,293 (“the ’293 patent”) and 7,125,905 (“the ’905 patent”) 

Nature of the Case and Issue(s) Presented:  Sutent is indicated for the treatment of advanced renal cell carcinoma, gastrointestinal stromal tumor after disease progression on or intolerance to imatinib mesylate, and progressive, well-differentiated pancreatic neuroendocrine tumors in patients with unresectable locally advanced or metastatic disease. Prior to trial, Mylan stipulated that its ANDA products would infringe Pfizer’s patents.  Therefore, the only issue at trial was whether the asserted claims of the ’293 and ’905 patents were invalid as obvious. After a four day bench trial the court found that the patents were not invalid.     

Why Pfizer Prevailed:  The court first considered Mylan’s argument that a nearly identical analogue of sunitinib was disclosed in a prior-art patent application no. 99/61422 (“the ’422 application). The ’422 application disclosed a large number of oxindoles, which included an analogue structurally similar to sunitinib, known as dimethyl sunitinib.  The sole difference between sunitinib and the analogue compound was that dimethyl sunitinib has a dimethylamine solubilizing group while sunitinib has a diethylamine group. In addition to dimethyl sunitinib, the ’422 application also disclosed approximately 1,200 other possible combinations. Despite Mylan’s arguments to the contrary, the court found that the process of going from dimethyl sunitinib to sunitinib to sunitinib malate would have required significant guesswork and variation of parameters in order to achieve the claimed compound. Given the volume of possible combinations and the additional subsequent chemical alterations necessary to arrive at the claimed compound, it would not have been obvious to alter dimethyl sunitinib in the manner suggested by Mylan.

Next, the court turned its attention to a group of lead compounds that Mylan argued would have served as logical starting points in the formulation of sunitinib malate. Mylan, in addition to establishing that a person of ordinary skill in the art (“POSA”) would have selected a given lead compound, would also need to prove that the modifications necessary to arrive at the claimed compound would have been obvious to a POSA. Mylan identified SU5416, SU5408 and dimethyl sunitinib as potential lead compounds. The court acknowledged that SU5416 represented a breakthrough in anti-angiogenesis cancer treatment when it was first disclosed. But a POSA likely would have acknowledged its very significant shortcomings, such as a lack of oral bioavailability. Additionally, the court pointed to the fact that second-generation compounds had identified the importance of a propionic acid group, which was necessary for potency. SU5416 did not include such a group, and was therefore taught away from. Therefore, SU5416 would not have been selected as a lead compound. Concerning SU5408, the court agreed that this compound did demonstrate strong potency in vitro. But there was no corresponding in vivo data available to support its potency. The court found it persuasive that although compounds such as SU5416 made it to the clinical trial stage and yielded significant data, SU5408 did not even make it to the clinical-trial stage. Again, the court pointed to the fact that much more promising second-generation compounds were available in order to discredit Mylan’s argument that SU5408 would have served as a logical starting point in the synthesis of sunitinib malate.

Last, the court considered Mylan’s argument that dimethyl sunitinib would have served as an acceptable lead compound. Immediately, the court seized on the fact that dimethyl sunitinib as it existed in the previously addressed ’422 application was a mere hypothetical compound. The compound had no name, had no chemical structure, had never actually been synthesized, and had no data demonstrating its properties. The court rejected Mylan’s position that dimethyl sunitinib would be an acceptable lead compound due to a “logic chain” described by its expert. Instead, the court concluded that a POSA would not have ignored actual, synthesized compounds with actual data in favor of a hypothetical, never-created compound as a lead.

Although Mylan had failed to establish a prima facie case of obviousness, the court nonetheless considered Pfizer’s evidence of objective indicia of non-obviousness.

The court found the activity of sunitinib compared with the previous clinical candidates, SU5416 and SU6668, was certainly much more potent with respect to in vitro data. The court also pointed to the incorporation of malate salt into the compound.  Evidence established that sunitinib malate had superior properties across the board compared to other salts, and such properties made it possible to commercialize sunitinib. The court concluded that a POSA would not have expected sunitinib malate to outperform the other salts in all categories. The court also found that sunitinib malate satisfied a long-felt need for the treatment of renal cell carcinoma and pancreatic neuroendocrine tumors. The evidence demonstrated that sunitinib malate provided greatly improved clinical outcomes for renal-cell-carcinoma patients, and represented a huge paradigm shift for the treatment of pancreatic neuroendocrine tumors. Sutent was also a commercial success. Sutent remains the dominant drug for renal cell carcinoma treatment, maintaining nearly fifty percent of the market six years after its launch, with almost twice as much market share as the nearest competitor. Moreover, Sutent is Pfizer’s largest revenue-generator among its oncology drugs, and its revenues have exceeded expenses each year it has been on the market. Also, Sutent is on pace to exceed its investment costs within ten years, while the average drug takes fifteen to sixteen years to reach this milestone. Finally, the court noted that several prior failed attempts at creating an effective anti-angiogenesis drug created a general sense of skepticism as to whether the concept could work in practice. The court found evidence that Sutent was a breakthrough in the industry, and was widely praised by researchers and doctors, to be persuasive.

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