IP Law Daily, PATENT—D. N.J.: Revised label for generic pulmonary hypertension drug may implicitly induce infringement, (Apr 17, 2014)

By Cheryl Beise, J.D.

In a lawsuit filed by United Therapeutics Corp. (“UTC”) challenging Sandoz, Inc.’s plans to produce a generic version of UTC’s REMODULIN® pulmonary hypertension drug, Sandoz failed to show that its revised product instruction label avoided infringement, the federal district court in Newark, New Jersey has ruled (United Therapeutics Corp. v. Sandoz, Inc., April 15, 2014, Sheridan, P.). UTC raised factual questions regarding whether the label induced infringement by implicitly instructing use of UTC’s patented method.

UTC markets and sells treprostinil sodium injection under the brand name REMODULIN® for use in the treatment of pulmonary arterial hypertension, a rare life- threatening disease which narrows the arteries of the lungs and slowly deprives the body of oxygen. UTC owns three patents—United States Patent Nos. 5,153,222 (the '222 patent); 6,765,117 (the '117 patent); and 7,999,007 (the '007 patent)— that are listed in the FDA’s Orange Book in connection with treprostinil sodium injection.

In December 2011, Sandoz filed an abbreviated new drug application (“ANDA”) with the FDA, seeking approval to market and sell a generic form of UTC’s patented Remouludin in 10mg/mL dosage form. In December 2012, Sandoz filed an amendment to its ANDA seeking approval for three additional dosage concentrations.

UTC contended that Sandoz infringed claim 23 of the '007 patent, directed to pharmaceutical preparations of REMODULIN®. UTC further asserted that Sandoz infringed and induced infringement of asserted method Claims 1-5, 7-17, and 19- 21 of the '007 patent because Sandoz’s generic Remodulin label encouraged doctors to practice the claims of the '007 patent.

Before the court was Sandoz’s motion for summary judgment that its revised label for generic Remodulin did not infringe or induce others to infringe the '007 patent.

Proposed instruction label. ANDA applicants may file a so-called “section viii statement” asserting that the generic manufacturer will market the drug only for methods of use not covered by the brand’s patent and proposing a label that excludes (“carves out”) still-patented methods of use.

In its initial ANDA application, Sandoz proposed a label for generic Remodulin that copied the instructions contained in UTC’s REMODULIN® label. UTC’s label explicitly instructs physicians and end-users to dilute the product with “Sterile Water for Injection, 0.9% Sodium Chloride Injection or Flolan Sterile Diluent for Injection” prior to intravenous infusion. Flolan® is a product marketed by GlaxoSmithKline for treating pulmonary hypertension. The “Flolan Sterile Diluent” is a solution used to dilute Flolan prior to intravenous infusion. Because the Flolan diluent is a glycine 10 buffer, its use would directly implicate the asserted method claims of the '007 patent, the court explained.

Recognizing its error, Sandoz amended its ANDA to substitute a revised proposed label that deleted all references to the Flolan diluent. Sandoz submitted a Section viii statement, stating that the '007 patent does not claim uses for the treprostinil sodium ANDA products for which Sandoz is seeking FDA approval.

Sandoz argued that its amended label for its treprostinil sodium products did not infringe or induce infringement of high pH glycine buffers because it “carved out” the use of a buffer in subcutaneous infusion and recommended aseptic techniques when preparing/administering treprostinil (wiping hands with alcohol rather than using the Flolan diluent).

UTC argued that Sandoz’s revised instruction label continued to induce infringement because it used words and phrases that implicitly instructed use of the sterile Flolan diluent. Specifically, the label indicated that the intravenous route of a treprostinil injection was associated with certain bloodstream infections and that sepsis may be fatal. Such language allegedly alerted a practitioner to research the bloodstream infections for precautionary measures.

The Sandoz label also referred to a CDC survey about such infections. According to UTC, the CDC survey easily led practitioners to review the medical research concerning the CDC survey, including an article that recommends using the Flolan diluent to prevent bloodstream infections. The label therefore circuitously led practitioners to infringe the '007 patent.

The court found that UTC’s argument presented a factual question as to whether Sandoz implicitly induced infringement through deliberate indifference. Sandoz’ motion for summary judgment was denied.

The case is Nos. 12-CV-01617 and 13-CV-316.

Attorneys: David C. Kistler (Blank Rome, LLP) for United Therapeutics Corp. Christina Lynn Saveriano (Hill Wallack, LLP) for Sandoz, Inc.

Companies: United Therapeutics Corp.; Sandoz, Inc.

Cases: Patent NewJerseyNews