In its non-precedential decision in INO Therapeutics LLC v. Praxair Distribution Inc., the Federal Circuit agreed with the district court that method of treatment claims reciting “excluding” specific patients from treatment were ineligible for patenting under 35 USC § 101. Stakeholders in the personalized medicine space likely are hoping that this decision will be cabined to the specific claims at issue, and not herald new scrutiny of more typical personalized medicine claims.

The INOMax® Patents At Issue 

The underlying ANDA litigation involved a number of Orange Book-listed patents for INOMax®, including U.S. Patent No. 8,282,966, U.S. Patent No. 8,293,284, U.S. Patent No. 8,795,741, U.S. Patent No. 8,431,163, and U.S. Patent No. 8,846,112. INOMax® is a nitric oxide delivery system indicated for use to improve oxygenation and reduce the need for extracorporeal membrane oxygenation in neonatal patients with hypoxic respiratory failure associated with clinical or echocardiographic evidence of pulmonary hypertension. 

The Federal Circuit cited claim 1 of the ’741 patent as representative:

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.

I previously wrote about the district court decision in this article.

The Federal Circuit Decision

The Federal Circuit decision was authored by Chief Judge Prost and joined by Judge Dyk. Judge Newman dissented from the subject matter (non)eligibility determination.

Interestingly, the majority’s § 101 analysis starts with noting the state of the art. The majority also emphasizes from the outset that the claimed method involves non-treatment of a subset of patients:

Applying this [Alice/Mayo] test, we agree with the district court that claim 1 of the ’741 patent is ineligible.It is undisputed that treatment of infants experiencing hypoxic respiratory failure with iNO gas has existed for decades.The inventors observed an adverse event that iNO gas causes for certain patients. The patent claim does no more than add an instruction to withhold iNO treatment from the identified patients; it does not recite giving any affirmative treatment for the iNO-excluded group, and so it covers a method in which, for the iNO-excluded patients, the body’s natural processes are simply allowed to take place.Consequently, the claim here is directed to the natural phenomenon. The claim, apart from the natural phenomenon itself, involves only well-understood, routine, and conventional steps. 

Diving into step one of the Alice/Mayo two-step analysis, the majority opinion states that the “natural phenomenon here” is that “[a] neonate patient’s body will react to iNO gas in a certain way depending on whether or not the patient has a congenital heart condition called LVD.” The majority finds that the claims are “directed to” the “observation” of that natural phenomenon and “then doing nothing but leaving the natural processes taking place in the body alone for the group of LVD patients.” The majority disagrees that the recited treatment of non-LVD supported eligibility, because the recited step was “a well-known dosage,” that was conceded to be “not innovative.” 

As for step two of the Alice/Mayo analysis, the majority stated: 

In essence, claim 1 boils down to an instruction to doctors: when treating neonatal patients with iNO gas, take into account their natural reaction to iNO gas. Do not give iNO gas to patients with LVD; otherwise, proceed with treatment. Any other steps are either necessary to manifest the natural law or are undisputedly routine and conventional.

*****

Therefore, whether viewed individually or as an ordered combination, the claims here do not recite a patent-eligible application under the second step of Mayo/Alice.

Thus, the majority affirmed the district court’s finding that the method of treatment patents are invalid under 35 USC § 101, with this qualification:

While § 101 precludes bare monopolies on natural phenomena, new and inventive methods of treatment in personalized medicine remain patent eligible. We conclude that the specific claims here are ineligible. But we emphasize the narrowness of our holding today, which is limited to the particular claims at issue and is driven by the particular circumstances here.

Judge Newman’s Dissent

Judge Newman disagreed with the majority’s approach under the Alice/Mayo framework.

The method that is described and claimed does not exist in nature; it was designed by and is administered by humans. …. The majority does not acknowledge that the claimed multi-step method of treatment of hypoxic respiratory failure does not occur in nature. The majority improperly separates the claims into old and new steps, describes some claim steps as a “natural phenomenon” and some steps as “well-understood, routine, and conventional steps,” and avoids the requirement that a claimed invention is considered as a whole.

Judge Newman also highlights the majority decision as a departure from Federal Circuit precedent that “has been reasonably consistent in holding that methods of medical treatment are eligible for patenting.” Judge Newman reminds the majority (and the rest of us) that patents incentivize, rather than impede, scientific advances:

Patents provide the economic incentive for medical scientists and industries to devise new treatments to serve the afflicted public. My colleagues’ holding that such inventions are broadly ineligible for patenting, will simply add disincentive to medical advance. 

Limiting The Reach Of This Decision 

Despite Judge Newman’s concerns, the majority opinion does include several statements that should limit the reach of the decision from more typical personalized medicine claims, including: 

• “[The patent] covers a method in which, for the iNO-excluded patients, the body’s natural processes are simply allowed to take place.”

• “In effect, the claim is directed to detecting the presence of LVD in a patient and then doing nothing but leaving the natural processes taking place in the body alone for the group of LVD patients.”

• “[T]he 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.”

• “[A] claim not to treat—i.e., not to disturb these naturally-occurring physiological processes within the LVD patient’s body—risks monopolizing the natural processes themselves.”

• “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.”

• “Here, by contrast [to Vanda], the invention is not focused on changing the physiological state of the patient to treat the disease.”

• “Mallinckrodt did not develop a new use for an old drug that provides a therapeutic benefit. The claimed method here recites an old use of an old drug. Then it proposes no use.”