Found in Nature, Claimed as an Invention: Why ‘Isolated NR’ Wasn’t Enough

Can a naturally occurring compound become patentable simply because it has been isolated? 

A company may identify a naturally occurring substance with useful properties, extract it from its natural environment, and formulate it into a commercial product. But does separating that substance from the material in which it naturally occurs make the substance patent-eligible? 

Under U.S. patent law, isolation alone is not enough. The central question in a product-of-nature analysis is whether the claimed subject matter has markedly different characteristics from its naturally occurring counterpart. The answer depends on the actual subject matter defined by the claims and the evidence in the record. 

1. What does ‘markedly different characteristics’ mean? 

The phrase is rooted in the Supreme Court’s subject-matter eligibility decisions, including Diamond v. Chakrabarty, 447 U.S. 303 (1980), and Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576 (2013). It is not a checklist with a fixed numerical threshold. It asks whether the claimed product is meaningfully different from what exists in nature, rather than merely being discovered, extracted, purified or isolated. 

Relevant differences may involve structure, composition, properties or function. These are ways to examine the claimed subject matter; they are not separate mandatory elements that every patent claim must satisfy. 

2. The landmark example: Diamond v. Chakrabarty 

In Diamond v. Chakrabarty, the Supreme Court considered a genetically engineered bacterium from the genus Pseudomonas. The bacterium contained multiple stable energy-generating plasmids, each providing a separate hydrocarbon-degradation pathway. 

The technical significance was not simply that the bacterium had been removed from its natural environment. Its genetic composition had been altered. The resulting organism could break down multiple components of crude oil, a capability the Court described as not possessed by any naturally occurring bacteria. 

The Court concluded that the claimed bacterium had markedly different characteristics from any found in nature and had the potential for significant utility. Chakrabarty is a landmark decision because it demonstrates that a human-made living organism may fall within patent-eligible subject matter when it possesses characteristics markedly different from naturally occurring organisms. 

3. Why Chakrabarty is different from merely isolating a natural substance 

The important distinction is between changing the claimed subject matter and merely separating a natural substance from other material. Chakrabarty involved an engineered organism with a changed genetic arrangement and resulting capabilities. It was not a case in which the inventor simply isolated an existing natural organism. 

4. ChromaDex v. Elysium: Why isolation alone was not enough 

The ChromaDex litigation is one of the clearest modern illustrations of a natural-product claim that failed not because the science was weak, but because the claims, as construed, did not carry the differences the patentee relied on. ChromaDex, Inc. and the Trustees of Dartmouth College (together, ChromaDex) asserted U.S. Patent Nos. 8,197,807 (the ’807 patent) and 8,383,086 (the ’086 patent) against Elysium Health, Inc. in the District of Delaware (No. 1:18-cv-01434-CFC-JLH, Chief Judge Colm F. Connolly). Both patents claim dietary supplements containing isolated nicotinamide riboside (NR), a form of vitamin B3, that increase NAD+ biosynthesis upon oral administration. 

The natural baseline was ordinary cow’s milk. It was undisputed that milk contains NR only in trace amounts (ChromaDex put the figure at about one part per million), that this NR is bound to the lactalbumin whey protein and is not bioavailable, and that milk nonetheless increases NAD+ biosynthesis because of the tryptophan it contains. The inventor’s asserted contribution was the discovery that NR isolated from those other components, and in particular unbound from the whey protein, increases NAD+ biosynthesis when taken orally (’807 patent col. 4 ll. 24–31). 

4.1 Procedural timeline 

4.2 The claims at issue 

Claim 1 of the ’807 patent, treated as representative of both patents, reads: 

1. A composition comprising isolated nicotinamide riboside in combination with one or more of tryptophan, nicotinic acid, or nicotinamide, wherein said combination is in admixture with a carrier comprising a sugar, starch, cellulose, powdered tragacanth, malt, gelatin, talc, cocoa butter, suppository wax, oil, glycol, polyol, ester, agar, buffering agent, alginic acid, isotonic saline, Ringer’s solution, ethyl alcohol, polyester, polycarbonate, or polyanhydride, wherein said composition is formulated for oral administration and increases NAD+ biosynthesis upon oral administration. 

The dependent claims added little that could separate the composition from milk: 

• ’807 claim 2: the NR “is isolated from a natural or synthetic source.” 
• ’807 claim 3: the formulation “comprises a tablet, troche, capsule, elixir, suspension, syrup, wafer, chewing gum, or food.” 
• ’086 claim 2: the pharmaceutical composition of claim 1 wherein the NR “is isolated from a natural or synthetic source.” The district court construed “pharmaceutical composition” broadly, as a composition that can be used to improve or prolong the health or well-being of humans or other animals. 

Notice what claim 1 does not say. It recites no amount or concentration of NR, no purity, no stability or shelf-life property, no statement that the NR is free of protein binding, and no link between the NR and the NAD+ increase. The function element is satisfied if the composition as a whole increases NAD+ biosynthesis, whatever the cause. 

4.3 Claim construction: three versions of “isolated” 

The term “isolated [NR]” was construed three different ways in this dispute. The difference between them goes a long way toward explaining the outcome. 

That construction carried directly into the § 101 analysis. On summary judgment, the district court held that the construction “in no way requires that the NR in the claimed composition be stable, bioavailable, sufficiently pure, or have a therapeutic effect,” and that the asserted claims are “simply not expressed in terms of stability, bioavailability, or purity; nor do they rely in any way on changes that result from the isolation of NR.” Relying on ChargePoint, the court said it would “decline to import details not claimed.” 

The Federal Circuit took the same point further in ChromaDex I. Because the NR need be separated only from “some” of the other source components, it could remain bound to the lactalbumin whey protein, so the claims “do not necessarily require that the isolated NR be bioavailable.” ChromaDex did not challenge the construction on appeal. 

Would the 25% figure have saved the claims? The district court thought not. In its 2024 Fee Order it noted ChromaDex’s stipulation and observed that “the outcome of this case would not have changed had [the court] adopted the purity requirement in the construction of ‘isolated NR’ originally proposed by ChromaDex.” The reason lies in the Federal Circuit’s analysis: a purity floor would have answered the structural point but not the others. The claims would still have required no quantity of NR, would still not have tied the NAD+ increase to NR, and milk would still have satisfied the functional element through tryptophan. The drafting point is that a limitation that lives only in a claim construction position is a fragile thing. If 25% purity mattered, it needed to be in the claim language. 

4.4 Element-by-element comparison with milk 

The Federal Circuit compared each element of claim 1 with natural milk, relying on facts the parties agreed: milk contains NR, tryptophan and lactose, and the tryptophan in milk treats NAD+ deficiency. Its conclusion was that “the only difference between at least one claimed embodiment and natural milk is that the NR is isolated.” 

Sources: ChromaDex I, 59 F.4th 1280 (citing J.A. 10095–96); district court Mem. Op. (Sept. 21, 2021). The “Distinguishing?” column for claims 2 and 3 is Rightium’s reading; neither court analysed them separately. 

There is one correction worth noting. The district court said it was undisputed that NR in milk enhances NAD+ biosynthesis. ChromaDex pointed out that this was wrong, and Elysium conceded the point; the record included Elysium’s own statement that “one can’t eat enough of anything” containing trace NR to raise NAD+ levels. The Federal Circuit held the error harmless (ChromaDex I, n.4), because claim 1 requires only that the composition increase NAD+ biosynthesis, not that the NR be the cause. That is the claim language doing the damage: milk met the function element through a different molecule. 

4.5 The characteristics that were not accepted as distinguishing 

ChromaDex put forward a series of differences between isolated NR and NR in milk. Its brief said the claimed compositions “contain isolated NR that is stable, bioavailable, and sufficiently pure that the compositions can be administered orally to deliver NR to the cells of an animal and exert therapeutic effect” (D.I. 278 at 6). Each asserted difference was rejected, and almost always for the same underlying reason: it was not in the claims. 

Sources: ChromaDex I, 59 F.4th 1280, 1284–85 (Fed. Cir. 2023); ChromaDex v. Elysium, No. 18-1434-CFC-JLH, Mem. Op. at 6–13 (D. Del. Sept. 21, 2021); Fee Order, 2024 WL 5105618, at *1. The “What the claim lacked” column is Rightium’s drafting observation, not a holding of either court. 

4.6 The contrast with Natural Alternatives 

ChromaDex’s main argument was that its claims resembled the beta-alanine supplement claims upheld in Natural Alternatives International, Inc. v. Creative Compounds, LLC, 918 F.3d 1338 (Fed. Cir. 2019). The Federal Circuit explained why the comparison failed: 

In Natural Alternatives, the court reasoned functionally under Chakrabarty: the natural product had been isolated and incorporated into a dosage form in an amount that produced a defined effect. ChromaDex’s claims had the isolation and the dosage form, but not the amount or the attribution. 

4.7 What the October 2026 decision adds 

The 2026 appeal concerned attorneys’ fees, not eligibility, but it sharpens the claim-drafting lesson. The district court had treated Myriad as dispositive and found ChromaDex’s position so weak that it “st[oo]d out” from the dozens of other § 101 challenges it had seen, noting that ChromaDex’s summary-judgment opposition mentioned Myriad only once. The Federal Circuit reversed the $9,151,133 award. In its words, it was “legal error to treat Myriad as the beginning and the end of the patent-eligibility analysis.” 

Resolving ChromaDex’s position required three further inquiries, each of which turned on what the claims said: 

• whether the claims require any specific quantity of isolated NR, and whether they attribute the NAD+ increase to it; 
• whether, under the construction of “isolated [NR],” the NR must be separated from lactalbumin and so be bioavailable; and 
• whether milk, through tryptophan rather than its trace NR, itself increases NAD+ biosynthesis. 

ChromaDex had real evidence. Its expert, Dr. Sobol, opined that the claimed compositions “have significant utility to be used in ways that NR appearing in nature cannot” (J.A. 3314–27). The 2026 panel accepted that the argument was serious enough to defeat a fee award. It still lost, because the claim language did not commit to the features that would have made the composition markedly different from milk. The decision is nonprecedential and does not alter ChromaDex I. 

The point is not that NR can never have different properties after isolation, or that the courts made a universal scientific finding about every isolated NR preparation. They assessed the claims before them, using the claim construction and evidentiary record in that case, and concluded that those claims did not establish the markedly different characteristics required to distinguish the claimed compositions from their natural counterpart. 

5. The drafting lesson: define the claimed distinction 

Chakrabarty and ChromaDex illustrate why the claims matter. A patent specification may describe technical advantages, experimental results or intended benefits. But those statements do not automatically become limitations of the claims. The claims define the legal scope of the invention. 

When an applicant relies on a distinction from nature, the application should identify the natural baseline, explain the technical feature that makes the claimed subject matter different, and provide disclosure and evidence supporting that feature. Where the distinction depends on a particular composition, structure, quantity, biological activity or functional relationship, the claims must be examined to determine whether they actually define it. 

In ChromaDex, each of the ten asserted differences in section 4.5 was argued from the specification, expert evidence or a claim-construction position, and none appeared in the claim text. Every entry in the “What the claim lacked” column is a candidate limitation: a recited amount, a purity or binding state, a measurable stability property, or a function tied to the natural product itself. These limitations narrow the claim and must be supported in the specification, but they are what turns a technical advantage into a claimed characteristic. 

6. Questions for R&D and patent teams 

• What is the closest naturally occurring counterpart to the proposed invention? 
• What specific structural, compositional, physical or functional characteristic distinguishes the claimed subject matter? 
• Can the asserted difference be measured, observed or otherwise demonstrated? 
• Does the specification provide adequate support for the asserted characteristic? 
• Do the claims actually define the feature relied upon to distinguish the invention from nature? 
• Does the claim scope extend to embodiments that may lack the asserted distinguishing characteristic? 
• Are the asserted benefits merely described in the specification, or are the relevant technical features captured by the claims? 

The Rightium takeaway 

Isolation is not, by itself, the same as invention. The relevant question is whether the claimed subject matter has characteristics markedly different from those found in nature. 

Chakrabarty demonstrates a landmark example of an engineered organism with a distinct genetic arrangement and resulting capabilities. ChromaDex demonstrates the difficulty of relying on isolation and an asserted biological benefit when the claims, as construed, do not establish the necessary distinction. 

For patent drafting, the practical discipline is to identify the natural baseline, define the technical distinction, support it in the specification, and ensure that the claims accurately capture the subject matter for which protection is sought. This does not guarantee eligibility; novelty, non-obviousness, written description, enablement and the other statutory requirements remain separate questions. 

Authorities 

• Diamond v. Chakrabarty, 447 U.S. 303 (1980). 
• Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576 (2013). 
• Natural Alternatives International, Inc. v. Creative Compounds, LLC, 918 F.3d 1338 (Fed. Cir. 2019). 
• ChromaDex, Inc. v. Elysium Health, Inc., No. 18-1434-CFC-JLH, Memorandum Opinion (D. Del. Sept. 21, 2021) (summary judgment of invalidity under § 101). 
• ChromaDex, Inc. v. Elysium Health, Inc., 59 F.4th 1280 (Fed. Cir. 2023) (ChromaDex I). 
• ChromaDex, Inc. v. Elysium Health, Inc., No. CV 18-1434-CFC, 2024 WL 1255520 (D. Del. Mar. 25, 2024) (exceptional-case decision). 
• ChromaDex, Inc. v. Elysium Health, Inc., No. CV 18-1434-CFC, 2024 WL 5105618 (D. Del. Aug. 20, 2024) (Fee Order). 
• ChromaDex, Inc. v. Elysium Health, Inc., No. 2025-1227 (Fed. Cir. Oct. 30, 2026) (nonprecedential) (reversing § 285 fee award). 
• Elysium Health Inc. v. Trustees of Dartmouth College, IPR2017-01795, Paper 39 (P.T.A.B. Jan. 16, 2019), aff’d (Fed. Cir. 2020). 
• Also cited: ChargePoint, Inc. v. SemaConnect, Inc., 920 F.3d 759 (Fed. Cir. 2019); Synopsys, Inc. v. Mentor Graphics Corp., 839 F.3d 1138 (Fed. Cir. 2016); Genetic Technologies Ltd. v. Merial L.L.C., 818 F.3d 1369 (Fed. Cir. 2016); Rapid Litigation Management Ltd. v. CellzDirect, Inc., 827 F.3d 1042 (Fed. Cir. 2016). 

Editorial scope: This article addresses the natural-product eligibility and claim-construction issues. The October 30, 2026 fee decision is discussed only for what it says about the eligibility analysis; its § 285 standards are outside the scope of this piece. Record citations (J.A., D.I.) are as given in the court opinions.