The PTAB recently addressed the limits on strategies to patent drug labeling, canceling claims directed to a method of supplying a pharmaceutical product where the method includes a step of providing certain “information” to the medical provider. According to the PTAB, the claimed step of providing the information is entitled to no patentable weight under the “printed matter” doctrine where it is not functionally related to other elements of the claimed method. Specifically, even if the claim says that the information is “sufficient to” cause some effect (e.g., for a medical provider to avoid treating a patient) there is no functional relationship with the claim if the claim doesn’t recite that effect. Praxair Distribution Inc. v. Mallinckrodt Hospital Prods. IP Ltd., IPR2015-00529.

Mallinckrodt markets an inhaled vasodilator (a blend of nitric oxide and nitrogen) under the name INOmax®. The product was initially FDA-approved in 1999. More recently, a clinical study revealed that patients with pre-existing left ventricular dysfunction had an increased risk of experiencing serious adverse events when treated with the product. This information led to an FDA label change that included warnings and precautions relating to patients having pre-existing left ventricular dysfunction, and to the patent application that issued as U.S. Patent No. 8,846,112. Praxair petitioned for inter partes review of all claims 1-19 of the patent, and the PTAB instituted trial on § 102(a) and § 103(a) grounds. Only claim 9 survived the IPR, as described below.

The independent claims (1, 7, 12, and 14) generally recite: (a) supplying a cylinder containing compressed nitric oxide gas to a medical provider; and (b) providing the medical provider with information and recommendations. Claims 1 and 9 (depending from 7) are illustrative:

  1. A method of providing pharmaceutically acceptable nitric oxide gas, the method comprising:

obtaining a cylinder containing compressed nitric oxide gas in the form of a gaseous blend of nitric oxide and nitrogen;

supplying the cylinder containing compressed nitric oxide gas to a medical provider responsible for treating neonates who have hypoxic respiratory failure, including some who do not have left ventricular dysfunction;

providing to the medical provider

(i) information that a recommended dose of inhaled nitric oxide gas for treatment of neonates with hypoxic respiratory failure is 20 ppm nitric oxide and

(ii) information that, in patients with pre-existing left ventricular dysfunction, inhaled nitric oxide may increase pulmonary capillary wedge pressure (PCWP), leading to pulmonary edema, the information of (ii) being sufficient to cause a medical provider considering inhaled nitric oxide treatment for a plurality of neonatal patients who (a) are suffering from a condition for which inhaled nitric oxide is indicated, and (b) have pre-existing left ventricular dysfunction, to elect to avoid treating one or more of the plurality of patients with inhaled nitric oxide in order to avoid putting the one or more patients at risk of pulmonary edema.

  1. A method of providing pharmaceutically acceptable nitric oxide gas, the method comprising: obtaining a cylinder containing compressed nitric oxide gas in the form of a gaseous blend of nitric oxide and nitrogen; supplying the cylinder containing compressed nitric oxide gas to a medical provider responsible for treating neonates who have hypoxic respiratory failure, including some who do not have pre-existing left ventricular dysfunction; and providing to the medical provider (i) information that a recommended dose of inhaled nitric oxide gas for treatment of neonates with hypoxic respiratory failure is 20 ppm nitric oxide, (ii) information that patients who have pre-existing left ventricular dysfunction and are treated with inhaled nitric oxide may experience pulmonary edema, and (iii) a recommendation that, if pulmonary edema occurs in a patient who has pre-existing left ventricular dysfunction and is treated with inhaled nitric oxide, the treatment with inhaled nitric oxide should be discontinued.
  1. The method of claim 7, further comprising: performing at least one diagnostic process to identify a neonatal patient who has hypoxic respiratory failure and is a candidate for inhaled nitric oxide treatment; determining prior to treatment with inhaled nitric oxide that the neonatal patient has pre-existing left ventricular dysfunction; treating the neonatal patient with 20 ppm inhaled nitric oxide, whereupon the neonatal patient experiences pulmonary edema; and in accordance with the recommendation of (iii), discontinuing the treatment with inhaled nitric oxide due to the neonatal patient’s pulmonary edema.

Following Federal Circuit precedent (including In re Distefano, 808 F.3d 845 (Fed. Cir. 2015) and King Pharms., Inc. v. Eon Labs, Inc., 616 F.3d 1267 (Fed. Cir. 2010)), the PTAB concluded that the step of “providing . . . information” should be given no patentable weight because it lacks a functional relationship with the remaining claim elements (the “obtaining” and “supplying” steps).

The PTAB considered and rejected the patent owner’s argument’s attempting to distinguish King and In re Kao, 639 F.3d 1057 (Fed. Cir. 2011). In King, according to the patent owner, the step of providing information of about the effect of food did not change the actual method of taking the drug with food. Likewise, in Kao, according to the patent owner, the step of providing information about a correlation between renal impairment and bioavailability did not change the administration of the drug. In contrast, the patent owner argued its patent claims explicitly recite that the information is “sufficient to cause a medical provider . . . to elect to avoid treating one or more . . . patients with inhaled nitric oxide” and, thus, that recitation transforms the process of administering the product. For all claims other than claim 9, the PTAB rejected the relevance of the recitation to the remaining claim elements. In particular, the PTAB pointed out that for all other claims the information does not transform the remaining elements of the claimed method, because the claimed method steps (e.g., “obtaining” and “providing”) are the same regardless of whether the medical provider is informed about the risks. With the “providing . . . information” step out of the picture for patentability, and remaining claim steps directed to purely mental exercises and conventional steps, the petitioner’s prior art evidence led to unpatentability under § 102(a) and/or § 103(a).

Claim 9, in contrast, explicitly recites steps of treating a patient and, in accordance with a recommendation provided with the product, discontinuing the treatment following a specific adverse event. The PTAB found a functional relationship between the recommendation and the remaining method steps because claim 9 requires discontinuing treatment in accordance with the recommendation. Because the prior art lacked a teaching or suggestion to discontinue treatment following the particular adverse event recited in the claim, claim 9 was not shown to be unpatentable.

While claim 9 of the ‘112 patent survived this IPR challenge, Praxair has not discontinued its efforts to invalidate the claim. It recently filed a new IPR petition (IPR2016-00781) that is based on additional prior art, and the PTAB’s institution decision is still pending.