It's not often that we write about pharmaceutical patents on this blog, and even less often that we blog here about PTAB decisions. The former is a function of the Federal Circuit's decision in Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals Int'l Ltd., 887 F. 3d 1122 (Fed. Cir. 2018) (holding that virtually all method of treatment patents automatically comply with Section 101); the latter is a function of the inability to challenge patents for noncompliance with Section 101 in an inter partes review, which is limited to certain prior-art challenges.
As more patents become eligible for post-grant review — which permits a broader array of challenges, including for lack of compliance with Section 101 — we are likely to see more PTAB decisions addressing Section 101. In this post, we write about one such example.
Tramiprosate and its prodrug, Val-APS, are under study for treatment of Alzheimer's Disease (AD). U.S. Patent 11,191,742 (the '742 patent) claims methods of treating a subset of AD patients with such compounds, — specifically, those patients with two copies of a gene known to increase the risk of AD (APOE4/4) who show only mild impairment based on their score on the Mini-mental State Examination (MMSE), on which higher scores mean less impairment. Claims 1 and 10 are illustrative of the claimed methods:
1. A method of treating Alzheimer's Disease in a subject, the method comprising administering to the subject a pharmaceutical composition comprising [Val-APS] or a pharmaceutically acceptable salt thereof, in an amount effective to reduce cognitive decline, only if the subject is determined to (i) be APOE4/4 homozygous; and (ii) have a baseline [MMSE] score of ≥22, wherein the MMSE was performed within sixty days prior to the first administration of the composition.
10. A method of selecting and treating a patient suffering from Alzheimer's disease comprising the steps of:
(a) selecting the patient if the patient is both APOE4/4 homozygous and has a baseline [MMSE] score of ≥22, wherein the MMSE was performed within sixty days prior to the first administration of the composition; and
(b) administering to the selected patient a pharmaceutical composition comprising [Val-APS] or a pharmaceutically acceptable salt thereof, in an amount effective to reduce cognitive decline.
These and other claims of the '742 patent were challenged on a multitude of grounds in PGR2022-00051. We address here only the Section 101 challenge.
Under the familiar Section 101 standard, the petitioner alleged that the claims were directed to a natural law and abstract idea (Alice step one), without the addition of elements that transform the claims into an eligible application of an otherwise ineligible concept (Alice step two). Because the PTAB found that the claims passed muster under step one, it had no need to reach step two.
With respect to Alice step one, the petitioner sought to place the claims into the "natural law" box, characterizing them as merely reciting the "biological result of the patient's genetics and disease progression," rather than being the product of any human action. Not surprisingly, this argument foundered on the shoals of Vanda, which essentially held that method claims directed to administering a drug are per se patent-eligible because they alter the recipient's natural state.
As part of this argument, the petitioner also tried to characterize the claims as similar to those held ineligible in INO Therapeutics LLC v. Praxair Distribution Inc., 782 Fed. App'x 1001 (Fed. Cir. 2019), which we blogged about at the time here. In the INO Therapeutics case, however, the claims were directed to identifying the subset of patients who would be harmed by the recited treatment and not treating them. As we wrote then:
[T]he 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 [the contraindication] with the standard dose of iNO [the therapy at issue]—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.
In the present case, the petitioner argued that the claims of the '742 were analogous to those in INO Therapeutics in the sense that they called for dividing AD patients into two groups based on a natural law — those who met the claimed genetic and disease-state criteria for treatment and those who did not — and then withholding treatment from the second group (as the claims in INO Therapeutics required withholding treatment with iNO from patients with LVD).
The PTAB's rejection of this argument illustrates how obviousness considerations can be fundamental to the question of ineligibility under Section 101:
We also find the challenged claims to be distinguishable from those in INO, cited by Petitioner. In INO, the focus of the claims was the instruction not to treat certain patients who had a screening-identified increased risk of side effects, while administering iNO . . . gas to other patients as was done before. . . . In contrast, the current claims recite a method for selecting a certain sub-population of AD patients to affirmatively treat with [Val-APS]. The '742 patent discloses that this particular subgroup of AD patients (APOE4/4 homozygotes with a MMSE score of ) 22) surprisingly showed the highest efficacy and progressive increase in cognitive benefit with the administration of tramiprosate.
Decision at 16 (emphasis added). As can be seen from the emphasized portions of the PTAB's explanation, considerations that plainly pertain to obviousness clearly played a part.
In taking this approach to Section 101, the PTAB was following the lead of INO Therapeutics:
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.
* * *
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.
INO Therapeutics, 782 Fed. App'x at 1005, 1011. Could the second part of the above block quote from INO Therapeutics be rewritten to find the claims of the '742 patent ineligible? Consider the following hypothetical explication of why they fail:
In essence, claim 1 boils down to an instruction to doctors: when treating patients with AD, take into account their genetics and disease severity. Do not give Val-APS to patients who are not homozygous for APOE4/4 or have a MMSE score of less than 22; otherwise, proceed with treatment. Any other steps are either necessary to manifest the natural law or are undisputedly routine and conventional.
We do not know from the PTAB's decision if the use of Val-APS to treat patients with AD was "routine and conventional" in the way that use of iNO was routine and conventional to treat neotates with respiratory failure: although the petitioner raised a number of obviousness challenges, the PTAB exercised its discretion under 35 U.S.C. § 325(d) to refrain from considering them on the ground that they had been considered by the Examiner during prosecution of the application that issued as the '742 patent.
Because denials of institution of PGR are not subject to appeal, the PTAB's decision is likely to be the last word on the '742 patent for the time being.
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