Nitric oxide – USA

On Aug 27, 2019, Federal Circuit affirmed district court’s decision which found some patents ineligible & some non-infringed in INOmax® case.

This appeal concerns to INO Therapeutics & Mallinckrodt’s (Plaintiff), U.S. Patent Nos. 8,282,966, 8,293,284, 8,795,741, 8,431,163, and 8,846,112 (“heart failure patents” or “HF patents”) & U.S. Patent Nos. 8,573,209, 8,776,794, 8,776,795, 9,265,911 and 9,295,802 (“delivery system infrared patents” or “DSIR patents”). These patents are listed in Orange Book for INOmax®. Praxair (Defendant) filed ANDA with USFDA seeking approval to market Noxivent, a generic form of 100 and 800 ppm nitric oxide gas for inhalation. Plaintiff sued defendant in Delaware court. District of Delaware after bench trial held all claims of the HF patents ineligible under 35 USC 101 and all claims of the DSIR patents not infringed.

Ineligibility under 35 USC 101:

Claim 1 of the ’741 patent is representative. Claim 1 recites:

1. A method of treating patients who are candidates for inhaled nitric oxide treatment, which method reduces the risk that inhalation of nitric oxide gas will induce an increase in pulmonary capillary wedge pressure (PCWP) leading to pulmonary edema in neonatal patients with hypoxic respiratory failure, the method comprising:

(a) identifying a plurality of term or near-term neonatal patients who have hypoxic respiratory failure and are candidates for 20 ppm inhaled nitric oxide treatment;

(b) determining that a first patient of the plurality does not have left ventricular dysfunction;

(c) determining that a second patient of the plurality has left ventricular dysfunction, so is at particular risk of increased PCWP leading to pulmonary edema upon treatment with inhaled nitric oxide;

(d) administering 20 ppm inhaled nitric oxide treatment to the first patient; and

(e) excluding the second patient from treatment with inhaled nitric oxide, based on the determination that the second patient has left ventricular dysfunction, so is at particular risk of increased PCWP leading to pulmonary edema upon treatment with inhaled nitric oxide.

On appeal, Mallinckrodt argued that, the “exclusion” step is the reason the claims are not directed to a natural phenomenon as no treatment protocol had screened for reducing such an adverse event before. Federal Circuit, however, disagreed & said that claim 1 is “directed to” that observation about the natural phenomenon. As drafted, the claim instructs a physician to administer iNO gas to non-LVD patients as before, while now excluding the LVD patients. The exclusion step merely restates the natural law. Properly understood, this added step is simply an instruction not to act. Also, Mallinckrodt cannot dispute that the patented method does not propose a new way of treating LVD patients that leverages this discovery (e.g., by titrating the iNO dose). Instead, the claim simply requires that the patient not be treated with iNO.

Mallinckrodt further argued that claims cannot be directed to a natural phenomenon because they recite a treatment step. Specifically, claim 1 requires the affirmative act of “administering 20 ppm inhaled nitric oxide treatment”—a well-known dosage—to a patient without LVD. Federal Circuit again disagreed & said that a closer look at the claim language as a whole confirms that the focus of the invention is not on a new way of actually treating the underlying condition of hypoxic respiratory failure. Nor does it recite a way of reducing the risk of pulmonary edema while providing some level of treatment to those patients. Rather, the focus of the invention is screening for a particular adverse condition that, once identified, requires iNO treatment be withheld. Also, Mallinckrodt does not point to “any innovation other than its [purported] discovery of the natural law.”

Therefore, the claims here are readily distinguishable from other cases that actually integrate or leverage natural laws to an eligible method of treatment for a particular disease. The patent does not delve into the complexities of dosing to more effectively “treat” different classes of patients as in Vanda, Natural Alternatives, and Endo Pharmaceuticals—by leveraging knowledge about a natural correlation to understand what amounts of a particular drug prove therapeutic for each patient. Therefore, HF patents claims are ineligible under 35 USC 101.

Non-infringement of DSIR patents:

Claim 1 of the ’794 patent is representative of the device claims and reads:

1. A gas delivery device comprising:

a gas source to provide therapy gas comprising nitric oxide;

a valve attachable to the gas source, the valve including an inlet and an outlet in fluid communication and a valve actuator to open or close the valve to allow the gas through the valve to a control module that delivers the therapy gas comprising nitric oxide in an amount effective to treat or prevent hypoxic respiratory failure; and

a circuit including:

a memory to store gas data comprising one or more of gas identification, gas expiration date and gas concentration; and

a processor and a transceiver in communication with the memory to send and receive signals to communicate the gas data to the control module that controls gas delivery to a subject and to verify one or more of the gas identification, the gas concentration and that the gas is not expired.

On appeal with respect to DSIR patents, Mallinckrodt challenged issue with the district court’s interpretation of the “verify” term. Claim 1 of the ’794 patent requires the device “verify one or more of the gas identification, the gas concentration and that the gas is not expired.” The district court interpreted the claim term to require that the gas delivery system verify data about the actual gas in the “gas source” (i.e., the cylinder being used). Federal Circuit sided with district court & said that because Praxair’s delivery system (NOxBOXi) does not “verify” the gas either, it does not infringe the asserted claims. Mallinckrodt’s expert, Dr. Schaafsma, testified that the NOxBOXi’s gas data does not come from the gas source. Therefore, Praxair ANDA does not infringe the DSIR patents.