Chromadex, Inc. v. Elysium Health, Inc.

59 F.4th 1280

• Court: Court of Appeals for the Federal Circuit
• Decided: February 13, 2023
• Docket: 22-1116
• Status: Published

Opinion

Case: 22-1116 Document: 44 Page: 1 Filed: 02/13/2023

United States Court of Appeals for the Federal Circuit ______________________

CHROMADEX, INC., TRUSTEES OF DARTMOUTH COLLEGE, Plaintiffs-Appellants

v.

ELYSIUM HEALTH, INC., Defendant-Appellee ______________________

2022-1116 ______________________

Appeal from the United States District Court for the District of Delaware in No. 1:18-cv-01434-CFC-JLH, Chief Judge Colm F. Connolly. ______________________

Decided: February 13, 2023 ______________________

WILLIAM L. MENTLIK, Lerner, David, Littenberg, Krumholz & Mentlik, LLP, Cranford, NJ, argued for plain- tiffs-appellants. Also represented by RUSSELL W. FAEGENBURG, STEPHEN F. ROTH; ROBERT JASON FOWLER, CHRISTOPHER NEIL SIPES, ASHLEY MARIE WINKLER, Coving- ton & Burling LLP, Washington, DC.

JEREMY YOUNKIN, Foley Hoag LLP, Boston, MA, ar- gued for defendant-appellee. Also represented by DONALD ROSS WARE. ______________________ Case: 22-1116 Document: 44 Page: 2 Filed: 02/13/2023

Before PROST, CHEN, and STOLL, Circuit Judges. PROST, Circuit Judge. ChromaDex, Inc. (“ChromaDex”) and the Trustees of Dartmouth College (“Dartmouth”) (collectively, “Appel- lants”) appeal the decision of the U.S. District Court for the District of Delaware granting Elysium Health, Inc.’s (“Ely- sium”) motion for summary judgment that the asserted claims of U.S. Patent No. 8,197,807 (“the ’807 patent”) are directed to unpatentable subject matter under 35 U.S.C. § 101. 1 We affirm. BACKGROUND I The ’807 patent is directed to dietary supplements con- taining isolated nicotinamide riboside (“NR”), a form of vit- amin B3 naturally present—in non-isolated form—in cow’s milk and other products. 2 See ’807 patent col. 27 ll. 42–45. Animal cells convert ingested NR into the coenzyme nico- tinamide adenine dinucleotide, or NAD+. NAD+ deficien- cies can cause diseases in both animals and humans. The asserted claims are claims 1–3 of the ’807 patent. Representative claim 1 recites: 1. A composition comprising isolated nicotinamide riboside in combination with one or more of trypto- phan, nicotinic acid, or nicotinamide, wherein said combination is in admixture with a carrier

1 Appellants also sought review of the district court’s invalidation of claim 2 of U.S. Patent No. 8,383,086. The voluntary dismissal of a related appeal mooted that part of the case. 2 For the sake of brevity, we use the word “milk” in the rest of this opinion to describe natural cow’s milk. Case: 22-1116 Document: 44 Page: 3 Filed: 02/13/2023

CHROMADEX, INC. v. ELYSIUM HEALTH, INC. 3

comprising a sugar, starch, cellulose, powdered tragacanth, malt, gelatin, talc, cocoa butter, sup- pository wax, oil, glycol, polyol, ester, agar, buffer- ing agent, alginic acid, isotonic saline, Ringer’s solution, ethyl alcohol, polyester, polycarbonate, or polyanhydride, wherein said composition is formu- lated for oral administration and increased NAD+ biosynthesis upon oral administration. II ChromaDex sells, among other products, dietary sup- plements in the form of pharmaceutical compositions of NR embodying the ’807 patent. It licenses the patent from Dartmouth. Appellants sued Elysium, a former Chro- maDex customer, for patent infringement in September 2018. The district court construed several claim terms; rel- evant here, the court construed “isolated [NR]” to mean “[NR] that is separated or substantially free from at least some other components associated with the source of [NR].” J.A. 22. Elysium moved for summary judgment, arguing that the asserted claims were invalid under 35 U.S.C. § 101, and the district court granted the motion. See ChromaDex, Inc. v. Elysium Health, Inc., 561 F. Supp. 3d 460 (D. Del. 2021). The district court concluded that the claims were directed to a natural phenomenon, namely, “compositions comprising isolated [NR], a naturally occurring vitamin present in cow milk.” Id. at 464 (cleaned up). It rejected ChromaDex’s argument that the characteristics of isolated NR purportedly different from naturally occurring NR— stability, bioavailability, sufficient purity, and therapeutic efficacy—render the claims patent-eligible, observing that none of those characteristics were part of the claims. Id. at 465. It concluded that “the decision to create an oral for- mulation of NR after discovering that NR is orally bioavail- able is simply applying a patent-ineligible law of nature.” Id. at 467. Case: 22-1116 Document: 44 Page: 4 Filed: 02/13/2023

The district court entered judgment of invalidity, and this appeal followed. 3 We have jurisdiction under 28 U.S.C. § 1295(a)(1). DISCUSSION I We review the district court’s grant of summary judg- ment under the law of the regional circuit, here the Third Circuit, which reviews such issues de novo. Junker v. Med. Components, Inc., 25 F.4th 1027, 1032 (Fed. Cir. 2022) (cit- ing Gonzalez v. Sec’y of Dep’t of Homeland Sec., 678 F.3d 254, 257 (3d Cir. 2012)). Summary judgment is appropri- ate when, drawing all reasonable inferences in the non- moving party’s favor, “there is no genuine dispute as to any material fact and the movant is entitled to judgment as a matter of law.” Fed. R. Civ. P. 56(a); Anderson v. Liberty Lobby, Inc., 477 U.S. 242, 255 (1986). Eligibility under § 101 may involve questions of fact but is, ultimately, a question of law that we review de novo. Nat. Alts. Int’l, Inc. v. Creative Compounds, LLC, 918 F.3d 1338, 1342 (Fed. Cir. 2019); Interval Licensing LLC v. AOL, Inc., 896 F.3d 1335, 1342 (Fed. Cir. 2018). “Whoever invents or discovers any new and useful pro- cess, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a

3 Appellants also challenge the district court’s orders granting-in-part Elysium’s motion to dismiss for lack of standing and denying its motion for leave to amend, as well as one of its claim constructions. The district court’s stand- ing order only dismissed claims of infringement based on activities alleged to have occurred on or after March 13, 2017, see J.A. 16–17, so the eligibility issue remained live. Because we affirm the district court’s invalidity judg- ment, we do not reach either the standing or the claim con- struction issues. Case: 22-1116 Document: 44 Page: 5 Filed: 02/13/2023

CHROMADEX, INC. v. ELYSIUM HEALTH, INC. 5

patent therefor, subject to the conditions and requirements of this title.” 35 U.S.C. § 101. “Laws of nature, natural phenomena, and abstract ideas,” in contrast, “are not pa- tentable.” Ass’n for Molecular Pathology v. Myriad Genet- ics, Inc., 569 U.S. 576, 589 (2013). II The parties agree that NR is naturally present in milk. It is undisputed that milk is a naturally occurring product that is not patent eligible. The parties also acknowledge that milk contains tryptophan and lactose, a sugar. And no one disputes that the tryptophan in milk treats NAD+ deficiencies. The claims are very broad and read on milk with only one difference as shown:

Element Milk

[1p] “A composition Milk is a composition. comprising”

[1a] “isolated [NR]” Milk contains NR, but the NR is not isolated. J.A. 10095.

[1b] “in combination Milk contains tryptophan with one or more of trypto- and nicotinamide. J.A. phan, nicotinic acid, or nico- 10095. tinamide”

[1c] “wherein said com- Milk is an admixture con- bination is an admixture taining a sugar (lactose). with a carrier comprising a J.A. 10096 sugar, starch, cellulose, powdered tragacanth, malt, gelatin, talc, cocoa butter, suppository wax, oil, glycol, polyol, ester, agar, buffering agent, alginic acid, isotonic Case: 22-1116 Document: 44 Page: 6 Filed: 02/13/2023

saline, Ringer’s solution, ethyl alcohol, polyester, pol- ycarbonate, or polyanhy- dride”

[1d] “wherein said com- Milk is formulated for oral position is formulated for administration. See J.A. oral administration” 10096.

[1e] “and increases Milk (through tryptophan) NAD+ biosynthesis upon increases NAD+ biosyn- oral administration.” thesis upon consump- tion. See J.A. 10096.

So the only difference between at least one embodiment within the scope of the claims and natural milk is that the NR in the former is isolated. The Supreme Court’s decisions in Myriad and Dia- mond v. Chakrabarty, 447 U.S. 303, 309 (1980), apply here. In Chakrabarty, the Court found eligible claims to a genet- ically engineered bacterium “capable of breaking down multiple components of crude oil.” 447 U.S. at 305, 318. No naturally occurring bacteria possessed the same prop- erty. Id. Accordingly, in the Court’s view, the “claim [was] not to a hitherto unknown natural phenomenon, but to a nonnaturally occurring manufacture or composition of matter—a product of human ingenuity having a distinctive name, character and use.” Id. at 309–10 (cleaned up). Be- cause “the patentee ha[d] produced a new bacterium with markedly different characteristics from any found in na- ture and one having the potential for significant utility,” the Court upheld the claims. Id. at 310. As in Myriad, under the circumstances presented here, the act of isolating the NR compared to how NR naturally exists in milk is not sufficient, on its own, to confer patent eligibility. See Myriad, 569 U.S. at 590–93. The claimed compositions remain indistinguishable from natural milk Case: 22-1116 Document: 44 Page: 7 Filed: 02/13/2023

CHROMADEX, INC. v. ELYSIUM HEALTH, INC. 7

because, other than separation from some other compo- nents, the isolated NR is no different structurally or func- tionally from its natural counterpart in milk. Chakrabarty defines the inquiry: to be patentable, the claimed composi- tion must “ha[ve] markedly different characteristics and have the potential for significant utility.” 447 U.S. at 310. Milk, like the claimed compositions, undisputedly “in- crease[s] NAD+ biosynthesis” upon oral administration. The claimed compositions do not exhibit markedly different characteristics from natural milk and are, therefore, inva- lid for claiming a patent-ineligible product of nature. Cf. Myriad, 569 U.S. at 579 (concluding “that a naturally oc- curring DNA segment is a product of nature and not patent eligible merely because it has been isolated” (emphasis added)). Our Natural Alternatives decision is particularly in- structive. There, we upheld, at the motion-to-dismiss stage, claims directed to dietary supplements containing beta-alanine. See 918 F.3d at 1341. We concluded that the patents there claimed “specific treatment formulations that incorporate[d] natural products” and that those for- mulations “ha[d] different characteristics and c[ould] be used in a manner that beta-alanine as it appears in nature cannot.” Id. at 1348. Specifically, the “natural products ha[d] been isolated and then incorporated into a dosage form”—“between about 0.4 grams to 16 grams”—“with par- ticular characteristics”—namely, to “effectively increase[] athletic performance.” Id. at 1348–49. Those markedly dif- ferent characteristics distinguished the claimed supple- ments from natural beta-alanine and preserved the claims’ validity. Id. at 1349. Here, in contrast, the asserted claims do not have char- acteristics markedly different from milk. Both the claimed compositions and milk “increase[] NAD+ biosynthesis upon oral administration.” Appellants argue that the claimed compositions are advantageous over milk because the iso- lation of NR allows for significantly more NAD+ Case: 22-1116 Document: 44 Page: 8 Filed: 02/13/2023

biosynthesis than is found in milk and that the large quan- tity of NR itself can alone increase NAD+ biosynthesis. But the asserted claims do not require any minimum quantity of isolated NR. Nor do these claims attribute the claimed increase in NAD+ biosynthesis to the isolated NR, requir- ing only that the composition increase NAD+ production. Because milk increases NAD+ biosynthesis, the claimed compositions do not possess characteristics markedly dif- ferent from those found in nature. To be sure, the claims cover several different composition embodiments, some of which are structurally different from milk. However, as noted above, the claims also encompass—as both parties agree—at least one embodiment that covers milk, except that the NR element is “isolated.” Because the claims are broad enough to encompass a product of nature, it is inva- lid under § 101. Appellants nonetheless argue that the claims, in fact, possess markedly different characteristics that render them patent-eligible. See Appellants’ Br. 28–31. They base this argument on two main points: (1) “NR is found in milk in only trace amounts,” i.e., one part per million; and (2) “what little NR is found in milk is not bioavailable” be- cause it is bound to the lactalbumin whey protein. Id. at 29. 4 The problem for Appellants is two-fold. First, as

4 Appellants also identify a factual error in the dis- trict court’s opinion. The court stated that it was “undis- puted that NR in milk . . . enhances NAD+ biosynthesis.” ChromaDex, 561 F. Supp. 3d at 465. Appellants correctly point out that the NR in milk does not enhance NAD+ bio- synthesis, that it argued as much to the district court, and that Elysium conceded the point. See, e.g., J.A. 10245 (Ely- sium admitting that “one can’t eat enough of anything [con- taining trace amounts of NR] to boost NAD+ levels”). That error was harmless, however, because the claims do not re- quire that the NR, specifically, increase NAD+ Case: 22-1116 Document: 44 Page: 9 Filed: 02/13/2023

CHROMADEX, INC. v. ELYSIUM HEALTH, INC. 9

discussed above, milk increases NAD+ biosynthesis (albeit because it contains tryptophan rather than because of the trace amounts of NR), and that is the only therapeutic ef- fect that the claims require. Second, the claims simply do not reflect the distinctions Appellants rely on: they do not require any specific quantity of isolated NR, and the dis- trict court’s construction for “isolated [NR],” which Appel- lants do not challenge on appeal, does not require that the NR be separated from the lactalbumin whey protein but only from “some of the other components associated with the source of [NR].” J.A. 22 (emphasis added). The claims, therefore, do not necessarily require that the isolated NR be bioavailable, meaning that the claimed compositions do not necessarily possess markedly different characteristics from milk, as they must to be patent-eligible. We conclude that the asserted claims lack markedly different characteristics from milk. They claim a product of nature and are not patent eligible. III The inquiry could end here—the Supreme Court in Myriad relied on Chakrabarty’s “markedly different char- acteristics” framework for analyzing whether the claimed compositions there were directed to a natural phenomenon; the Court never applied the Alice/Mayo two-step frame- work despite deciding the case after Mayo. See Myriad, 569 U.S. at 593–95; see also Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 573 U.S. 208, 217 (2014); Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 77–80 (2012). But if resort to Alice/Mayo is necessary, then at step one we conclude the asserted claims are directed to a product of nature for the reasons stated above, and at step two the claims lack an inventive step because they are directed to

biosynthesis; it is enough if the claimed composition accom- plishes that objective, and milk does so. Case: 22-1116 Document: 44 Page: 10 Filed: 02/13/2023

nothing more than compositions that increase NAD+ bio- synthesis, which is the very natural principle that renders the claims patent-ineligible. 5 Appellants identify only two possible inventive steps: “[1] recognizing the utility of NR for enhancing health and well-being and [2] the wisdom of isolating the NR to pro- vide concentrations higher than what occur naturally.” Ap- pellants’ Br. 31 (emphasis original). But recognizing the utility of NR is nothing more than recognizing a natural phenomenon, which is not inventive. See Myriad, 569 U.S. at 591. And the act of isolating the NR by itself, no matter how difficult or brilliant it may have been (although the specification makes clear that it was conventional), simi- larly does not turn an otherwise patent-ineligible product of nature into a patentable invention. See id. So the claims would likewise fail at step two. CONCLUSION We have considered Appellants’ remaining arguments and find them unpersuasive. As Appellants conceded at oral argument, our resolution of the patent-eligibility issue moots the standing question. For the reasons set forth

5 In Natural Alternatives, we purported to analyze the patent-eligibility of the claimed compositions under Al- ice/Mayo’s two-step framework. See Nat. Alts., 918 F.3d at 1342, 1348–49. But because we concluded that factual al- legations relating to the claimed compositions’ markedly different characteristics from natural beta-alanine pre- cluded judgment on the pleadings, the analysis function- ally examined only the Chakrabarty question. See id. at 1348. Indeed, in one prior case, we analyzed composition- of-matter claims under Myriad and Chakrabarty but ana- lyzed method claims under Mayo. Compare In re BRCA1- and BRCA2, 774 F.3d 755, 759–61 (Fed. Cir. 2014), with id. at 761–765. Case: 22-1116 Document: 44 Page: 11 Filed: 02/13/2023

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above, we affirm the district court’s judgment that the as- serted claims of the ’807 patent are invalid under 35 U.S.C. § 101. AFFIRMED