Case Name: United Therapeutics Corp. v. Sandoz, Inc., Civ. Nos. 12-cv-01617, 13-cv-316, 2014 U.S. Dist. LEXIS 121573 (D.N.J. Aug. 29, 2014) (Sheridan, J.)
Drug Product and Patent(s)-in-Suit: Remodulin® (treprostinil sodium); U.S. Patents Nos. 6,576,117 (“the ’117 patent”) and 7,999,007 (“the ’007 patent”)
Nature of the Case and Issue(s) Presented: UTC claimed that Sandoz induced infringement of the ’007 patent by instructing physicians to dilute its product for use intravenously. The asserted claim required a particular diluent to be used. UTC argued that the dosing instructions in the package insert informed physicians that the product may be delivered intravenously and that care should be given to avoid blood stream infections. As such, a physician would research the blood stream infection issue and uncover references from UTC instructing that dilution with Flolan is preferred to reduce blood stream infections.
Sandoz countered that its prescribing instructions do not induce infringement because there is no mention of the use of Flolan as the diluent, which was required by the asserted claims. The instructions merely inform a physician that use of diluent may be needed for intravenous delivery. Sandoz further argued that the ’007 patent was invalid as anticipated, obvious, and indefinite. Sandoz relied mainly on a single European patent application as the basis for its anticipation and obviousness defenses, arguing that the application taught all of the asserted limitations, and that those limitations related to killing gram negative bacteria and inhibiting gram positive bacteria were either inherent or combined with UTC’s disclosure of Flolan.
Next, UTC asserted that Sandoz infringed the ’117 patent under the doctrine of equivalents. The asserted claims were directed to manufacturing treprostinil with certain claimed intermediates. UTC argued that Sandoz’s method of manufacturing would result in substantially the same intermediates as claimed in the ’117 patent. Sandoz responded that it designed around the ’117 patent by using a PMB group, which allowed Sandoz to skip the separate de-protection step. Sandoz argued that the use of PMB made it easier to purify and characterize the intermediates. Moreover, Sandoz asserted that the ’117patent was invalid as anticipated and obvious. Sandoz argued that the prior-art patent taught the process of creating treprostinil in the claimed manner in the ’117 patent. Sandoz further argued that claimed process would have been obvious by modifying the patent with standard purification methods to reach the claimed treprostinil product.
The court found the ’007 patent valid and not infringed, but further found the ’117 patent valid and infringed.
Why UTC Prevailed: UTC proved by a preponderance of the evidence that Sandoz’s ANDA product infringed the ’117 patent under the doctrine of equivalents. The PMB group performed substantially the same function as the claimed limitation by protecting the phenolic oxygen molecule. Sandoz did not provide any differences with the use of PMB or the claimed limitation as it related to serving as a protective group. The PMB group performed the same function in substantially the same way as the claimed limitation as well. Particularly important to the court was the fact that Sandoz’s reaction and the claimed reaction used the same reagents, solvents, and reaction conditions. Finally, the court found that the substantially same result was obtained by both processes. In particular, both processes resulted in a “successful and scalable Pauson-Khand reaction.” This reaction results in a “successfully ring-closed tricyclic product with a protected phenol functional group.”
The court found the claims of the ’117 patent valid. It rejected Sandoz’s anticipation argument because the prior-art reference did not teach the process of obtaining the claimed product via stereo-selectivity. As for Sandoz’s obviousness defense, the court was persuaded by amount of secondary considerations of non-obviousness, including the failure of others, unexpected results, and commercial success of Remodulin.
Next, the court found that Sandoz did not induce others to infringe the ’007 patent because it did not instruct physicians to use the Flolan diluent as required by the claims. The court rejected UTC’s “scavenger hunt” argument that a physician would ultimately find the research from UTC. The test for induced infringement is whether the instructions require a physician to use the claimed method. Here, the instructions provided no mention of Flolan as a diluent. The general instruction to be concerned with blood stream infections was not an instruction to use Flolan as claimed in the ’007 patent.
Moreover, the claims of the ’007 patent are valid because the prior art relied on by Sandoz failed to teach at least three claim elements: (i) a “pharmaceutical composition;” (ii) “killing gram negative bacteria and inhibiting gram positive bacteria;” and (iii) “low buffer capacity.” The court also rejected Sandoz’s obviousness argument because the references did not teach element (ii) in any manner or provide a suggestion to one of skill that Sterile Diluent Flolan would provide such a function. In addition, there were significant secondary considerations of non-obviousness to refute the purported prior-art obviousness combination.
