September 3, 2019

Patents Nominally Directed to Method of Treatment Held Invalid as Claiming Law of Nature

Claims Instructed to Withhold Drug from Patients in whom it was Contraindicated
Holland & Knight Section 101 Blog
Charles A. Weiss

Most of the Section 101 cases discussed on this blog concern patents in the technology arts, which are commonly challenged on the ground that the claims are invalid because they are directed to an "abstract idea." This post concerns a pharmaceutical case, in which the Section 101 challenge was based on the argument that the claims were directed to a "law of nature."

By way of background, patents claiming methods of treating patients by administering pharmaceuticals have generally survived challenges under Section 101. For example, patents that direct treating patients with lower doses of a particular drug when lab tests show that those patients will be more sensitive than typical—for example because of a specific genetic variation that results in slow metabolism, or impaired renal function that results in slow elimination—were held by the Federal Circuit to claim patent-eligible subject matter. Vanda Pharms. Inc. v. West-Ward Pharms. Int'l Ltd., 887 F.3d 1117 (Fed. Cir. 2018); Endo Pharm. Inc. v. Teva Pharm. USA, Inc., 919 F.3d 1347 (Fed. Cir. 2019).

In a recent case, the Federal Circuit held that claims which were written in method-of-treatment format, but instructed to not treat patients with a drug that might cause them harm, were invalid as claiming laws of nature. INO Therapeutics LLC v. Praxair Distribution Inc., No. 2018-1019 (Fed. Cir. Aug. 27, 2019).

This case arose from the defendants' submission of an abbreviated new drug application (ANDA) seeking FDA approval to sell a generic formulation of the plaintiffs' inhaled nitric oxide (iNO) medical gas. For those who don't remember their chemistry, the formula for nitric acid is NO, while that for nitrous oxide (laughing gas) is N2O. They are distinct compounds with different physiological effects.

Nitric oxide is a vasodilator that can be useful for treatment of pulmonary hypertension, including in certain neonates with respiratory problems. However, giving it to infants with compromised heart function, specifically left ventricular dysfunction, was found to increase the risk of pulmonary edema. The patents at issue were directed to "solving" this problem by withholding iNO from neonates with the heart condition, although some of the claims were drafted more creatively by further reciting the step of administering iNO to those patients without the heart problem. The Federal Circuit quoted this claim as representative:

  1. A method of treating patients who are candidates for inhaled nitric oxide treatment . . . comprising:

(a) identifying a plurality of term or near-term neonatal patients who . . . are candidates for . . . inhaled nitric oxide treatment;

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

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

(d) administering . . . 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 . . . pulmonary edema upon treatment with inhaled nitric oxide.

U.S. Patent No. 8,795,741 (the '741 patent).

Translated from patentese, the claimed method was to determine which infants with breathing problems had LVD, and only treat infants without LVD with iNO.

Because the use of iNO for breathing problems was conventional, the only potentially inventive feature of the claims was to determine if an infant with respiratory problems also had LVD, and if so to refrain from treating that infant with iNO. This feature is even clearer in claims of some of the other asserted patents, such as this one:

  1. A method of reducing the risk of occurrence of pulmonary edema associated with . . . inhalation of 20 ppm nitric oxide gas, said method comprising: (a) performing echocardiography to identify a child in need of 20 ppm inhaled nitric oxide treatment for pulmonary hypertension . . .; (b) determining that the child . . . has left ventricular dysfunction, so is at particular risk of pulmonary edema upon treatment with inhaled nitric oxide; and (c) excluding the child from inhaled nitric oxide treatment based on the determination that the child has left ventricular dysfunction and so is at particular risk of pulmonary edema upon treatment with inhaled nitric oxide.

U.S. Patent No. 8,282,966 (the '966 patent).

The district court held the method claims invalid as being directed to unpatentable subject matter, and the Federal Circuit affirmed in a fully elaborated, but nonprecedential, opinion authored by Chief Judge Prost in which Judge Dyk joined. Judge Newman dissented.

The Federal Circuit opinion repeatedly noted that the claims were not directed to a method of giving a drug to treat a disease, but to an instruction to not give it. For example:

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.

Slip op. at 8-9. The court rejected the patentees' argument that the above-quoted claim of the '741 patent was directed to a "protocol" for "selective administration" of iNO, with the new step of not giving the drug to infants with LVD:

Properly understood, this added step is simply an instruction not to act. 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. Accordingly, the claim is directed to the natural phenomenon.

Id. at 10.

The Federal Circuit distinguished the result of the discovery at issue here—which is to refrain from giving the drug to patients in whom it may do more harm than good—with other method-of-treatment claims that were held to pass muster under Section 101. Specifically, the court explained that in each of the Vanda and Endo cases, the focus of the claims was treating the patient by administering the drug at issue in a different way, which used the law of nature underlying the discoveries "to produce a change in the natural state of the patient to treat a condition." Slip op. at 13.

Similarly, the claims at issue in a case involving nutritional supplements required administering sufficient amounts of a particular compound that was said to promote the endogenous production of creatine, thereby improving the user's athletic performance. Natural Alternatives Int'l, Inc. v. Creative Compounds, LLC, 918 F.3d 1338 (Fed. Cir. 2019). In that case, explained the INO Therapeutics opinion, "the claim used a particular dose of a substance to obtain a specific benefit by altering the subject's natural state. "Slip op. at 14 (internal citation omitted).

Although not mentioned by the Federal Circuit, another way to understand the outcome here is to note the similarity between the claims at issue and claims of diagnostic patents held invalid under Section 101. Specifically, while the preamble of the exemplary claim of the '741 patent recited that it was drawn to a "method of treating patients," the discovery behind the claim was associating the presence of LVD with the undesirability of administering iNO, i.e., not administering the identified treatment. Despite the preamble, then, the claim can be characterized as a method of acting on a diagnosis. This is more apparent from the above-quoted claim of the '966 patent, which unlike the exemplary claim of the '741 patent did not even require the step, albeit the conventional step, of administering iNO to infants with breathing problems who were not also diagnosed with LVD.

Understood in this manner, the claims at issue here are not too different for Section 101 purposes from those held invalid in Athena Diagnostics, Inc. v. Mayo Collaborative Services, LLC, 915 F.3d 742 (Fed. Cir. 2019), which concerned a method of diagnosing certain neurological diseases by detecting in the blood specific antibodies associated with them. In that case, the Federal Circuit distinguished Vanda by noting that Vanda concerned claims to a method of treatment:

Claiming a natural cause of an ailment and well-known means of observing it is not eligible for patent because such a claim in effect only encompasses the natural law itself [Athena]. But claiming a new treatment for an ailment, albeit using a natural law, is not claiming the natural law [Vanda].  

Athena, 915 F.3d at 752-53.

More simply, perhaps, the INO Therapeutics decision can also be understood as standing for the unremarkable proposition that applicants cannot rely merely on clever drafting—such as including the step of treating patients without LVD with the standard dose of iNO—to satisfy the demands of Section 101. Had the inventors' come up with an unconventional way of using iNO in patients with LVD, such as giving a reduced dose of iNO or coadministering it another drug that avoided the risk of pulmonary edema while preserving the benefits of iNO, claims directed to such methods would likely have fit comfortably within the Vanda/Endo line of cases holding that methods of treatment that change the body's natural state do not impermissibly claim a law of nature.

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