Section 101 Screens Out Claims of Using Biomarkers to Identify Drugs That May Cause Rare Disorder

Lysosomal storage disorders are a group of inherited diseases that range from treatable (Fabray Disease and Gaucher disease) to fatal (Niemann-Pick disease and Tay-Sachs disease). Drug-induced phospholipidosis (DIP) is mechanistically related to some of these diseases but, as the name suggests, caused by certain drugs. Drugs known to cause DIP include some antibiotics, antidepressants and cardiac medications. Because the ability of any given drug to cause DIP is not readily predictable from its chemical structure alone, identification of drugs (or drug candidates) capable of causing DIP is valuable for safety assessments.

The Patent at Issue

The patent at issue in Nextcea Inc. v. Lipotype, Inc., 2026 WL 323348 (D. Mass. Feb. 6, 2026), claimed methods of testing compounds for their ability to cause DIP. U.S. Patent 8,313,949 (the '949 patent). It was based on the inventors' discovery that a specific biomarker with four isoforms correlates with certain lysosomal storage disorders, including DIP. Historically, phospholipidosis was identified by examining a subject's tissues using electron microscopy, a process described in the patent as "invasive, relatively non-quantitative, expensive, and time consuming." The patented invention offered a "less invasive approach for detecting phospholipidosis," exploiting the "unexpected discovery" that levels of the biomarker's isoforms "correlate differentially with the phospholipidosis induced by different drugs and inherited lysosomal storage disorders."

The claims of the '949 patent called for administering the compound of interest to an animal, measuring the level of specified biomarkers in the animal's cells, and comparing the results to a control. For example, claim 1, with the chemical names of the biomarkers elided, recited:

1. A method for evaluating the activity of a test compound to induce phospholipidosis in a target subject, comprising

obtaining (1) a test sample from a test subject that has been administered a test compound …,

determining the level of each of a group of biomarkers in the test sample …, and

comparing the level of each biomarker with a corresponding predetermined level for the same biomarker, the predetermined level being obtained … from a control sample from a control subject who has not been administered the test compound …,

wherein the test compound is determined to have the activity to induce phospholipidosis in the target subject if the level of any of the group of biomarkers is at or above the corresponding pre-determined level.

Regular readers of this blog and students of Section 101 will question if the omitted portions from the above quotation – or any of the dependent claims – recited specific assay methods or other analytical techniques to quantify the amounts of the specified biomarkers. They did not. Nor did any of the claims require doing anything with the claimed "determination," such as treating a patient with a particular drug to reverse or ameliorate the effect of DIP that may have been identified by measurement of the claimed biomarkers. Claim 14 (discussed below) required using the measured results to manage treatment of a patient but did not specify how such management was to be carried out.

The Court's Analysis

Applying the two-step Alice/Mayo framework, the district court concluded that the claims were directed to patent-ineligible natural phenomena and lacked the inventive concept necessary to transform them into patentable applications of those phenomena.

Step One: Directed to a Natural Law

At Alice/Mayo step one, the court found that the claims were "directed to little more than 'multistep methods for observing' natural phenomena," i.e., the correlation between elevated biomarkers and lipid storage disorders. It rejected the patentee's argument that because the claims were directed to "a laboratory procedure undertaken in preclinical settings such as the unnatural process of drug development," as opposed to natural processes occurring within patients or subject, they were not directed to natural phenomena, writing that "whether a natural phenomenon occurs in clinical settings or within a patient's body does not affect its patentability."

In making this determination, the court rejected the patentee's argument that measuring the specific biomarkers recited in the claims was not conventional. It distinguished Rapid Litigation Management Ltd. v. CellzDirect, Inc., 827 F.3d 1042 (Fed. Cir. 2016), in which the Federal Circuit held that claims directed to methods of creating preparations of liver cells resistant to freeze-thaw cycles were not ineligible because even if the claims exploited the inventors' discovery of a natural law, they went beyond that by virtue of claiming a "new and useful laboratory technique." Slip op. at 9 (quoting 827 F.3d at 1048).

The court separately considered claim 14, which recited using results of the biomarker measurement to inform treatment of patients:

14. A method for managing patient treatment comprising

identifying a patient under a treatment suspected to induce phospholipidosis in the patient,

obtaining a test sample from the patient,

determining the level of each of a group of biomarkers in the test sample …, and

comparing the level of each biomarker with a corresponding pre-determined level for the same biomarker, the pre-determined level being obtained from a control sample from a control subject who has phospholipidosis,

wherein the patient is determined to be not suitable for the treatment if the level of any of the group of biomarkers is at or above the corresponding predetermined level.

The patentee argued that claim 14 was patent eligible because it was directed to a method of managing treatment of patients, more specifically, to "managing treatment for a specifically identified condition, phospholipidosis, suspected to be induced by a particular treatment in a particular patient receiving that treatment." Slip op. at 12. With this characterization, the patentee tried to bring claim 14 into the type of method-of-treatment claims that the Federal Circuit has largely exempted from the strictures of Section 101. See, e.g., Endo Pharms Inc. v. Teva Pharms. USA, Inc., 919 F.3d 1347 (Fed. Cir. 2019); Vanda Pharms. Inc. v. West-Ward Pharms. Int'l Ltd., 887 F.3d 1117 (Fed. Cir. 2018). The district court did not bite, distinguishing claim 14 from those cases on the basis that "here, unlike the claims in Vanda and Endo, no particular treatment of patient is specified." Slip op. at 12.

The district court did not, but seemingly could have, also pointed to INO Therapeutics LLC v. Praxair Distribution Inc., 782 Fed. Appx. 1001 (Fed. Cir. 2019), in which the Federal Circuit distinguished claims that called for not treating patients from conventional method of treatment claims held per se eligible in Vanda and Endo. As discussed in a prior post concerning that decision, claims that exploited a natural law to not administer a drug to patients in whom it was contraindicated were ineligible because they merely told clinicians about the natural law without requiring treatment. The Nextcea court's analysis follows a similar logic: claim 14's "wherein" clause reciting that the patient "is determined to be not suitable for the treatment" lacks the requirements in Vanda and Endo to administer particular dosages of specified drugs to patients with the recited characteristics. Indeed, as the court observed, claim 14 did not even go so far as requiring discontinuation of treatment. Slip op. at 14 ("Claim 14 stops short of prescribing any particular treatment at all – much less a dosage of zero. Rather, its use of the term 'determined' suggests on that the results of the claimed method will divulge whether the patient is 'suitable for treatment'; it does not instruct a doctor to take any particular step after making this determination or to reduce a treatment dosage to zero." Like the claims in Mayo, claim 14 "simply tell[s] a doctor about the relevant natural laws, at most adding a suggestion that he should take those laws into account when treating his patient." Slip op. at 14 (quoting Mayo, 566 U.S. at 78).

Step Two: No Inventive Concept

Having found the claims directed to patent-ineligible material, the court turned to whether they contained an inventive concept (which, if present, would make them patent eligible). The patentee argued that measuring the specific biomarkers recited in the claims was not conventional. Although the court did not reject the factual premise of this argument, it disagreed with the patentee's conclusion that measuring an unconventional biomarker was necessarily inventive even if the measurement itself was made using standard laboratory techniques. Citing Athena Diagnostics, Inc. v Mayo Collaborative Services, LLC, 915 F.3d 743, 751 (Fed. Cir. 2019), the court distinguished measuring an unconventional parameter from using an unconventional measurement technique, writing that the '949 patent "amount to no more than instructing users to adapt conventional methods" to measure the recited biomarkers. Slip op. at 16.

Discussion

The court's observation that the analytical methods enumerated in the '949 patent's specification to measure the biomarker were conventional echoes the Federal Circuit's approach in CareDx, Inc. v. Natera, Inc., 40 F.4th 1371 (Fed. Cir. 2022), where the specification's characterization of recited techniques as "routine and conventional" precluded an argument at step 2 that such techniques supplied an inventive concept. Id. at 1378 ("the written description is replete with characterizations of the claimed techniques in terms that confirm their conventionality"). The specification of the '949 patent did not use such explicit language, but its identification of well-known analytical methods – mass spectrometry, chromatography, ELISA, and others – as suitable for practicing the claimed methods undermined the patentee's argument that the claims included an inventive concept at step 2.

A point of interest is the court's approach to the eligibility issue through the lens of "natural law" as opposed to "abstract idea." To be sure, the natural law approach is in some ways a more comfortable (and certainly more conventional) fit for Alice step 1 – or perhaps better called Mayo step 1 – than the abstract idea approach typically applied outside the life sciences arts. But this case also shows how some types of biomedical claims could just as well be viewed at Alice step 1 through the abstract idea lens. Specifically, the claims here also fit the "collect data, analyze data, report result" structure of claims that are held to be directed to an abstract idea at Alice step 1 in the technological arts. See, e.g., Electric Power Group, LLC v. Alstom S.A., 830 F.3d 1350, 1353 (Fed. Cir. 2016) (holding that claims focusing on "collecting information, analyzing it, and displaying certain results of the collection and analysis" are directed to abstract idea at Alice step 1).

Although the '949 patent was not directed to diagnostic methods in the conventional sense, the nature of the inventors' discovery (unconventional application of biomarkers) and outcome (ineligible as directed to a natural law without a sufficient inventive concept) fit comfortably – or uncomfortably, depending on one's point of view – into the line of cases invalidating diagnostic patents. The primary difference, in this case without a distinction, between the '949 patent and those diagnostic patents was the focus here on using the inventors' discovery to identify drugs with the potential to cause DIP instead of using it to diagnose patients with lysosomal storage disorders. As such, this case can be understood as a continuation of the line of cases applying an unforgiving Section 101 scrutiny to diagnostic method patents. See, e.g., Cleveland Clinic Found. v. True Health Diagnostics LLC, 859 F.3d 1352, 1361 (Fed. Cir. 2017) (claims that "start and end with naturally occurring phenomena with no meaningful non-routine steps in between" are "directed to a natural law"). Like the cases that came before it, this decision illustrates the difficulty of enforcing diagnostic method patents directed to correlations between biomarkers and disease, even when the underlying scientific discovery is inventive and clinically useful.