Regenxbio Inc., Trustees of the University of Pennsylvania v. Sarepta Therapeutics, Inc., Sarepta Therapeutics Three, LLC

United States Court of Appeals
for the Federal Circuit
______________________
REGENXBIO INC., TRUSTEES OF THE
UNIVERSITY OF PENNSYLVANIA,
Plaintiffs-Appellants
v.
SAREPTA THERAPEUTICS, INC., SAREPTA
THERAPEUTICS THREE, LLC,
Defendants-Appellees
______________________
2024-1408
______________________
Appeal from the United States District Court for the
District of Delaware in No. 1:20-cv-01226-RGA, Judge
Richard G. Andrews.
______________________
Decided: February 20, 2026
______________________
SUSAN E. M ORRISON, Fish & Richardson PC, Wilming-
ton, DE, argued for all plaintiffs-appellants. Plaintiff-ap-
pellant REGENXBIO Inc. also represented by D EANNA
J EAN REICHEL , Minneapolis, MN.
J ULIE S. G OLDEMBERG, Morgan, Lewis & Bockius LLP,
Philadelphia, PA, for plaintiff-appellant Trustees of the
University of Pennsylvania. Also represented by AMY M.
D UDASH , Wilmington, DE.
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REGENXBIO INC. v. SAREPTA THERAPEUTICS, INC. 2
ROBERT B. WILSON, Quinn Emanuel Urquhart & Sulli-
van, LLP, New York, NY, argued for defendants-appellees.
Also represented by J AMES BAKER , ANASTASIA M.
F ERNANDS .
______________________
Before D YK, HUGHES , and STOLL , Circuit Judges.
STOLL , Circuit Judge.
REGENXBIO Inc. and The Trustees of the University
of Pennsylvania (collectively, “REGENXBIO”) filed a pa-
tent infringement suit in the United States District Court
for the District of Delaware against Sarepta Therapeutics,
Inc. and Sarepta Therapeutics Three, LLC for infringing
claims 1–9, 12, 15, and 18–25 of U.S. Patent
No. 10,526,617. Both parties moved for summary judg-
ment of patent eligibility under 35 U.S.C. § 101. The dis-
trict court granted Sarepta’s motion and held the claims
ineligible under § 101 as directed to a natural phenome-
non. Because we hold the claims are not directed to a nat-
ural phenomenon, we reverse the district court’s decision
and remand the case for further proceedings.
BACKGROUND
I
Genetic disorders—like cystic fibrosis, hemophilia, and
sickle cell anemia—are caused by mutations or deletions in
the sequences of nucleotides in one’s DNA. Gene therapy
allows the use of modified virus “vectors” to deliver a new
therapeutic gene (a “transgene”) that replaces the defective
or missing gene, treating or possibly even curing the dis-
ease by addressing the underlying genetic disorder. Host
cells can be engineered to contain plasmids, where a plas-
mid is a circular piece of DNA that is separate from the
chromosomes of the host cell, and the plasmid has the de-
sired transgene within it. A host cell can make multiple
copies of the plasmid and also proliferate to make more
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REGENXBIO INC. v. SAREPTA THERAPEUTICS, INC. 3
host cells. Plasmids can contain a capsid sequence, where
a capsid is the outer shell of a vector. These plasmids can
be purified, collected, and introduced into a mammalian
host cell, along with other plasmid DNA, to generate a gene
therapy vector.
The ’617 patent is titled “Method of Detecting and/or
Identifying Adeno-Associated Virus (AAV) Sequences and
Isolating Novel Sequences Identified Thereby,” and is di-
rected to genetically engineered host cells that contain
adeno-associated virus rh.10 sequences. U.S. Patent
No. 10,526,617 Title. The Background of the Invention ex-
plains that AAVs are nonenveloped viruses with single-
stranded DNA. It further explains that “AAV’s life cycle
includes a latent phase at which AAV genomes, after infec-
tion, are site specifically integrated into host chromosomes
and an infectious phase in which, following either adenovi-
rus or herpes simplex virus infection, the integrated ge-
nomes are subsequently rescued, replicated, and packaged
into infectious viruses.” Id. at col. 1 ll. 31–36. These “prop-
erties of non-pathogenicity, broad host range infectiv-
ity, . . . and potential site-specific chromosomal integration
make AAV an attractive tool for gene transfer.” Id. at col. 1
ll. 36–40. The Background of the Invention recognizes that
“[w]hat are desirable are AAV-based constructs for gene
delivery.” Id. at col. 1 ll. 52–53.
The inventors of the ’617 patent sought to develop such
constructs and specifically developed “molecules which uti-
lize the novel AAV sequences of the invention, including
fragments thereof, for production of molecules useful in de-
livery of a [transgene comprising a] heterologous gene or
other nucleic acid sequences to a target cell.” Id. at col. 17
ll. 15–19. In pursuit of this, the inventors created host cells
that “contain sequences encoding a novel AAV capsid”—
and a heterologous non-AAV sequence. Id. at col. 17 ll. 36–
37; see also id. at col. 17 ll. 42–45, col. 18 ll. 19–26.
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REGENXBIO INC. v. SAREPTA THERAPEUTICS, INC. 4
Claim 1 is representative for the purposes of this ap-
peal:
1. A cultured host cell containing a recombinant
nucleic acid molecule
encoding an AAV vp1 capsid protein having a se-
quence comprising amino acids 1 to 738 of SEQ ID
NO: 81 (AAVrh.10) or a sequence at least 95% iden-
tical to the full length of amino acids 1 to 738 of
SEQ ID NO: 81, wherein the recombinant nucleic
acid molecule further comprises a heterologous
non-AAV sequence.
Id. at col. 437 ll. 55–63.
The cultured host cells required by the claims are un-
disputedly human made. They do not exist in nature. No-
tably, a recombinant nucleic acid molecule is created by
chemically splicing together nucleic acid sequences from
two different organisms. Appellants’ Br. 5; see also Parker
Br. 11 (defining recombinant nucleic acids as “combining
genetic material from two different sources,” which are
used “to create new, human-made sequences” (citation
omitted)).1 And, as noted above, the claim term “heterolo-
gous” means coming from a different species.
1 Amicus brief filed by the Parker Institute for Can-
cer Immunotherapy, The J. David Gladstone Institutes,
and the Dana-Farber Cancer Institute. See ECF No. 27.
The amici further explain that creating recombinant DNA
is a multi-step process: (1) fragments of DNA are created,
for example, by using restriction enzymes chosen to cleave
DNA at specific sites in order to get the desired fragments;
(2) the desired DNA fragments are joined by DNA ligases;
(3) the recombinant nucleic acid sequence with the desired
DNA fragments is ligated into a plasmid that is used to
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REGENXBIO INC. v. SAREPTA THERAPEUTICS, INC. 5
II
REGENXBIO accused Sarepta of infringing claims 1–
9, 12, 15, and 18–25 of the ’617 patent based on Sarepta’s
use of the AAV variant rh.74 in cultured host cells to make
a gene therapy product referred to as SRP-9001, which
treats Duchenne muscular dystrophy. See REGENXBIO
Inc. v. Sarepta Therapeutics, Inc., No. 20-cv-1226-RGA,
2024 WL 68278, at *1 (D. Del. Jan. 5, 2024). Both parties
moved for summary judgment on whether the asserted
claims were eligible under 35 U.S.C. § 101. The district
court noted that there were no underlying factual disputes
pertaining to eligibility in this case and the parties agreed.
REGENXBIO, 2024 WL 68278, at *3.
The parties debated whether the claims disclose natu-
ral products and both analogized this case to Association
for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S.
576 (2013), in which the Supreme Court considered the el-
igibility of composition claims under the markedly differ-
ent characteristics test from Diamond v. Chakrabarty,
447 U.S. 303 (1980). Neither party asserted that the
claims are ineligible as an abstract idea or on any other
grounds.
Starting with the markedly different framework from
Chakrabarty, the district court noted that “[t]he ’617 pa-
tent’s claims disclose natural products, including the rh.10
transform a host cell; (4) the plasmid is then amplified by
growing colonies of the host cells; and (5) after amplifica-
tion, the recombinant DNA is extracted from the host cell
and purified. Parker Br. 12–13 (citations omitted). The
transformation of the host cell that occurs at step three al-
lows the cell to take up an exogenous nucleic acid sequence
via transfection, which is “the process of artificially intro-
ducing nucleic acids (DNA or RNA) into cells.” Parker
Br. 14–15 (citations omitted).
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REGENXBIO INC. v. SAREPTA THERAPEUTICS, INC. 6
sequence and a heterologous non-AAV sequence.”
REGENXBIO, 2024 WL 68278, at *4. The district court
then posited that in both Chakrabarty and Myriad the Su-
preme Court “highlight[ed] the importance of change” be-
tween naturally occurring subject matter and the claimed
composition. Id. at *5. The district court explained that in
Chakrabarty, “the invention was patentable because the
inventor genetically engineered bacteria to make the bac-
teria ‘capable of breaking down multiple components of
crude oil.’” Id. (quoting Chakrabarty, 447 U.S. at 305, 310).
Continuing, the district court explained that in Myriad,
“the inventor removed non-coding regions from naturally
occurring DNA sequences to create something new.” Id.
(citing Myriad, 569 U.S. at 594–95). Turning to claim 1 of
the ’617 patent, however, the district court determined
that none of the individual naturally occurring components
in the claims had been changed and that “combin[ing] nat-
ural products and put[ting] them in a host cell does not
make the invention patentable under § 101.” Id.
Instead, the district court determined that the claims
here were “similar to the ineligible claims in Funk Brothers
[Seed Co. v. Kalo Inoculant Co., 333 U.S. 127 (1948)],” be-
cause “[t]aking ‘two sequences from two different organ-
isms and put[ting] them together’ is no different than
taking two strains of bacteria and mixing them together.”
REGENXBIO, 2024 WL 68278, at *5 (third alteration in
original) (citation omitted). The district court further con-
sidered and disregarded that the claimed human-made ge-
netically engineered host cell possessed utility for gene
therapy because nothing in the claims discloses use of the
recombinant nucleic acid for a particular purpose.
The district court then considered whether the claims
recited an inventive concept under step two of the Al-
ice/Mayo framework. The district court determined the
claims lacked an inventive concept and “the claimed inven-
tion is made using well-understood, routine, and conven-
tional steps.” Id. at *6. The district court thus granted
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REGENXBIO INC. v. SAREPTA THERAPEUTICS, INC. 7
Sarepta’s summary judgment motion and held all asserted
claims of the ’617 patent ineligible under § 101.
REGENXBIO appeals. We have jurisdiction under
28 U.S.C. § 1295(a)(1).
D ISCUSSION
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 SRI Int’l, Inc. v. Cisco Sys., Inc., 930 F.3d 1295, 1306
(Fed. Cir. 2019)). Summary judgment is appropriate when,
drawing all reasonable inferences in the nonmoving 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 in-
volve 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); In-
terval 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 pa-
tent therefor, subject to the conditions and requirements of
this title.” 35 U.S.C. § 101. “Laws of nature, natural phe-
nomena, and abstract ideas,” in contrast, “are not patenta-
ble.” Myriad, 569 U.S. at 589 (citation omitted). An
overview of the Supreme Court’s decisions in Chakrabarty,
Funk Brothers, and Myriad, as well as our decision in Chro-
maDex, Inc. v. Elysium Health, Inc., 59 F.4th 1280
(Fed. Cir. 2023), is useful prior to considering
REGENXBIO’s claims.
In Chakrabarty, the Court held eligible claims directed
to a genetically engineered bacterium that possessed the
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REGENXBIO INC. v. SAREPTA THERAPEUTICS, INC. 8
advantage of being “capable of breaking down multiple
components of crude oil.” 447 U.S. at 305. Illustrative
claim 7 recited:
[7. A] bacterium from the genus Pseudomonas con-
taining therein at least two stable energy-generat-
ing plasmids, each of said plasmids providing a
separate hydrocarbon degradative pathway.
Id. at 305; see also Application of Chakrabarty, 571 F.2d
40, 41–42 (CCPA 1978). No naturally occurring bacteria
possessed the same property for breaking down crude oil.
Chakrabarty, 447 U.S. at 305. 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) (citation omitted). Because “the patentee
ha[d] produced a new bacterium with markedly different
characteristics from any found in nature and one having
the potential for significant utility,” the Court upheld the
claims. Id. at 310.
In Chakrabarty, the Court also distinguished the
claimed invention from that in Funk Brothers. Id. The
Court explained that, in Funk Brothers, “the patentee had
discovered that there existed in nature certain species of
root-nodule bacteria which did not exert a mutually inhib-
itive effect on each other” and “used that discovery to pro-
duce a mixed culture capable of inoculating the seeds of
leguminous plants.” Id. This was considered ineligible as
“only some of the handiwork of nature”:
Each of the species of root-nodule bacteria con-
tained in the package infects the same group of le-
guminous plants which it always infected. No
species acquires a different use. The combination
of species produces no new bacteria, no change in
the six species of bacteria, and no enlargement of
the range of their utility. Each species has the
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REGENXBIO INC. v. SAREPTA THERAPEUTICS, INC. 9
same effect it always had. The bacteria perform in
their natural way. Their use in combination does
not improve in any way their natural functioning.
They serve the ends nature originally provided and
act quite independently of any effort of the pa-
tentee.
Id. (quoting Funk Bros., 333 U.S. at 131). The Court dis-
tinguished Funk Brothers by emphasizing that, in
Chakrabarty, the patentee’s “discovery is not nature’s
handiwork, but his own; accordingly it is patentable sub-
ject matter under § 101.” Id.
The Court in Myriad later looked to both Chakrabarty
and Funk Brothers when considering the eligibility of two
sets of claims. The claims in the first set were directed to
isolating an individual’s BRCA1 and BRCA2
genes: “‘[1. A]n isolated DNA coding for a BRCA1 polypep-
tide,’ which has ‘the amino acid sequence set forth in SEQ
ID NO:2,’” and “SEQ ID NO:2 sets forth a list of
1,863 amino acids that the typical BRCA1 gene encodes.”
Myriad, 569 U.S. at 584 (citation omitted). As to this set of
claims, it was “undisputed that Myriad did not create or
alter any of the genetic information encoded in the BRCA1
and BRCA2 genes. The location and order of the nucleo-
tides existed in nature before Myriad found them. Nor did
Myriad create or alter the genetic structure of DNA.” Id.
at 590. The Court explained that “Chakrabarty is central
to this inquiry” of eligibility before concluding that “[i]n
this case, by contrast [to Chakrabarty], Myriad did not cre-
ate anything.” Id. at 590–91. Instead, as in Funk Brothers,
Myriad’s claims “fell squarely within the law of nature ex-
ception.” Id. at 591. While “Myriad found the location of
the BRCA1 and BRCA2 genes, . . . that discovery, by itself,
d[id] not render the BRCA genes ‘new . . . composition[s] of
matter.’” Id. (second alteration and second omission in
original) (quoting 35 U.S.C. § 101). The Court was not per-
suaded by Myriad’s reliance on its claims being directed to
isolating genes, reasoning that this did not render the
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REGENXBIO INC. v. SAREPTA THERAPEUTICS, INC. 10
claims eligible because they “are simply not expressed in
terms of chemical composition, nor do they rely in any way
on the chemical changes that result from the isolation of a
particular section of DNA.” Id. at 593.
In contrast to the claims directed to isolating the
BRCA1 and BRCA2 genes, the Court held Myriad’s second
set of claims directed to cDNA eligible. The relevant claim
language read, “[2. T]he isolated DNA of claim 1, wherein
said DNA has the nucleotide sequence set forth in SEQ ID
NO:1,” where SEQ ID NO:1 sets forth a sequence of cDNA
exons in the BRCA1 gene, rather than a full DNA sequence
containing both exons and introns.2 Id. at 584 (citation
omitted). The Court reasoned that:
cDNA does not present the same obstacles to pa-
tentability as naturally occurring, isolated DNA
segments. As already explained, creation of a
cDNA sequence from mRNA results in an exons-
only molecule that is not naturally occurring. Peti-
tioners concede that cDNA differs from natural
DNA in that “the non-coding regions have been re-
moved.” They nevertheless argue that cDNA is not
patent eligible because “[t]he nucleotide sequence
of cDNA is dictated by nature, not by the lab tech-
nician.” That may be so, but the lab technician un-
questionably creates something new when cDNA is
made. cDNA retains the naturally occurring exons
of DNA, but it is distinct from the DNA from which
it was derived. As a result, cDNA is not a “product
of nature” and is patent eligible under § 101 . . . .
2 “Only some DNA nucleotides . . . code for amino ac-
ids; these nucleotides are known as ‘exons.’ Nucleotides
that do not code for amino acids, in contrast, are known as
‘introns.’” Myriad, 569 U.S. at 581.
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REGENXBIO INC. v. SAREPTA THERAPEUTICS, INC. 11
Id. at 594–95 (alteration in original) (emphases added) (ci-
tations and footnote omitted).
In ChromaDex, our court followed Chakrabarty and
Myriad in determining the eligibility of claims directed to
the isolation of a vitamin—NR3—found in milk. The claims
recited “[a] composition comprising . . . isolated [NR]” in
combination with other elements also found in milk
“wherein said composition . . . increases NAD+[4] biosyn-
thesis upon oral administration.” ChromaDex, 59 F.4th
at 1283 (second alteration in original). In ChromaDex, it
was undisputed that the only structural difference between
the claims and naturally occurring milk was that the NR
in the claimed composition was isolated. Id. at 1283–84.
Our court explained that “Chakrabarty defines the in-
quiry: to be patentable, the claimed composition must
‘ha[ve] markedly different characteristics and have the po-
tential for significant utility.’” Id. at 1284 (alteration in
original) (quoting Chakrabarty, 447 U.S. at 310). We held
the claims ineligible because “the asserted claims do not
have characteristics markedly different from milk.” Id.
The patentee argued that the claimed composition recited
a marked difference from natural milk—i.e., that the isola-
tion of the milk vitamin NR allowed for significantly more
NAD+ biosynthesis than is found in milk. Id. However,
the court explained that natural milk has NAD+ biosynthe-
sis (albeit due to a different element in milk, tryptophan),
the asserted claims do not require any minimum quantity
of the isolated NR vitamin, and the claims do not attribute
the claimed increase in NAD+ biosynthesis to the isolated
3 NR stands for nicotinamide riboside, a form of vit-
amin B3. ChromaDex, 59 F.4th at 1281.
4 NAD+ stands for the coenzyme nicotinamide ade-
nine dinucleotide. ChromaDex, 59 F.4th at 1281. “NAD+
deficiencies can cause diseases in both animals and hu-
mans.” Id.
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REGENXBIO INC. v. SAREPTA THERAPEUTICS, INC. 12
vitamin NR. Id. at 1284–85. The court further analogized
the case to the gene isolation claims in Myriad, noting that,
“[a]s in Myriad, . . . the act of isolating the [vitamin] com-
pared to how [it] naturally exists in milk is not sufficient,
on its own, to confer patent eligibility.” Id. at 1284 (citing
Myriad, 569 U.S. at 590–93). Because “[t]he claimed com-
positions d[id] not exhibit markedly different characteris-
tics from natural milk[, they were], therefore, invalid for
claiming a patent-ineligible product of nature.” Id.
After focusing on the “‘markedly different characteris-
tics’ framework for analyzing whether the claimed compo-
sitions there were directed to a natural phenomenon,” the
court in ChromaDex noted that “[t]he inquiry could end.”
Id. at 1285. We pointed out that the Supreme Court has
“never applied the Alice/Mayo two-step framework [to such
claims,] despite deciding [Myriad] after Mayo.” Id. How-
ever, we opined that “if resort to Alice/Mayo is necessary,”
the claims in ChromaDex were directed to a product of na-
ture under step one for the reasons explained in the court’s
markedly different characteristics analysis. Id. We then
determined that, under step two, “the claims lack an in-
ventive step because they are directed to nothing more
than compositions that increase NAD+ biosynthesis, which
is the very natural principle that renders the claims pa-
tent-ineligible.” Id. at 1285–86.
Turning now to the composition claims at issue here,
as explained above, Chakrabarty defines our inquiry. We
thus ask whether the claimed host cells have “markedly
different characteristics” and have “the potential for signif-
icant utility” from that which is naturally occurring.
Chakrabarty, 447 U.S. at 310. In answering this inquiry
and considering the natural phenomenon exception, we
conclude that the claims here are more analogous to the
eligible claims in Chakrabarty and Myriad than the ineli-
gible claims in Funk Brothers, Myriad, and ChromaDex.
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REGENXBIO INC. v. SAREPTA THERAPEUTICS, INC. 13
It is uncontested that the claimed host cells include a
recombinant nucleic acid molecule that does not and can-
not exist in nature. Specifically, the claims require (1) “re-
combinant” nucleic acid, which means segments of nucleic
acid from one source are artificially manipulated or in-
serted into the nucleic acid of another source through gene
splicing; and (2) a nucleic acid molecule capable of encoding
a sequence at least 95% identical to an AAV rh.10 sequence
and a “heterologous” non-AAV sequence, where “heterolo-
gous” means from a different species. Thus, the recombi-
nant nucleic acid molecule must be spliced together via
human intervention from at least two different species to
meet the claim limitations.
Like the man-made plasmid combining four naturally
occurring bacteria in Chakrabarty, the claimed nucleic acid
molecules here, although containing naturally occurring
segments of DNA, are “not nature’s handiwork” and
“not . . . a hitherto unknown natural phenomenon, but . . .
a nonnaturally occurring manufacture or composition of
matter.” Chakrabarty, 447 U.S. at 309–10. Similarly, like
the cDNA claims in Myriad, “the lab technician unques-
tionably creates something new” when she splices together
the claimed recombinant nucleic acid molecule that en-
codes an AAV vp1 capsid protein and a heterologous non-
AAV sequence and inserts said molecule into a host cell.
Myriad, 569 U.S. at 595.
On the other hand, contrary to the district court’s hold-
ing, the claims here are distinguishable from those in Funk
Brothers. In concluding that the asserted claims are like
those in Funk Brothers, the district court found that
“[t]aking ‘two sequences from two different organisms and
put[ting] them together’ is no different than taking two
strains of bacteria and mixing them together.”
REGENXBIO, 2024 WL 68278, at *5 (second alteration in
original) (citation omitted). This analogy is flawed and in-
consistent with the undisputed scientific evidence in the
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REGENXBIO INC. v. SAREPTA THERAPEUTICS, INC. 14
record. The Court in Funk Brothers described the issues in
the field at the time and the patentee’s alleged invention:
There had been a few mixed cultures for field leg-
umes. But they had proved generally unsatisfac-
tory because the different species of the Rhizobia
bacteria produced an inhibitory effect on each other
when mixed in a common base, with the result that
their efficiency was reduced. Hence it had been as-
sumed that the different species were mutually in-
hibitive. [The patentee] discovered that there are
strains of each species of root-nodule bacteria
which do not exert a mutually inhibitive effect on
each other. He also ascertained that those mutu-
ally non-inhibitive strains can, by certain methods
of selection and testing, be isolated and used in
mixed cultures. Thus he provided a mixed culture
of Rhizobia capable of inoculating the seeds of
plants belonging to several cross-inoculation
groups.
333 U.S. at 129–30. As the Court pointed out, this may
have been an “important commercial advance,” but it was
no more than an improvement in packaging such that a
“farmer need not buy six different packages for six different
crops. He can buy one package and use it for any or all of
his crops of leguminous plants. And, . . . [this] also h[e]ld
advantages for the dealers and manufacturers by reducing
inventory problems and the like.” Id. at 131. But, the
Court continued, merely creating this type of commercial
advantage does not make something patentable. See id.
at 132.
In contrast, the claims here are not merely directed to
repackaging products of nature. Genetically engineering
two nucleic acid sequences from separate species into a sin-
gle molecule and then transforming a host cell in order to
incorporate that new molecule into it—thus fundamentally
creating a cell containing a molecule that could not form in
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REGENXBIO INC. v. SAREPTA THERAPEUTICS, INC. 15
nature on its own—is materially different from growing
more than one naturally occurring bacteria strain in a cul-
ture where none of the bacteria undergo any change from
their natural state.
In concluding otherwise, the district court ignored the
Supreme Court’s holding in Chakrabarty. In Chakrabarty,
the inventors transferred four different plasmids, each of
which were naturally occurring and capable of degrading
four different oil components, into a naturally occurring
bacterium. While the inventors genetically modified the
four plasmids to combine them, there is no indication that
the four plasmids transferred into the host bacterium were
otherwise themselves genetically engineered. See
Chakrabarty, 447 U.S. at 305 & n.1. Yet, the Court still
determined that the claimed bacterium was “a nonnatu-
rally occurring manufacture or composition of matter—
[i.e.,] a product of human ingenuity” that was “markedly
different” from the four individual plasmids. Id. at 309–10
(citation omitted). Chakrabarty thus undercuts the district
court’s reliance on the fact that “[t]he inventors of the
’617 patent . . . have not changed any of the claimed inven-
tion’s naturally occurring components,” like the “rh.10 se-
quences” and “non-AAV sequence.” REGENXBIO,
2024 WL 68278, at *5. Moreover, the district court’s anal-
ysis takes too narrow a view of the asserted claims by fo-
cusing on whether the individual components of the claim
were markedly different from what is naturally occurring
and failing to consider whether the claimed composition as
a whole was “not naturally occurring.” Myriad, 569 U.S.
at 594.5
5 Relatedly, the district court’s analysis of claim 20
from Association for Molecular Pathology v. USPTO,
689 F.3d 1303 (Fed. Cir. 2012) (“AMP”), although brief,
similarly contradicts its logic regarding the analogy
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REGENXBIO INC. v. SAREPTA THERAPEUTICS, INC. 16
Finally, although not required by Myriad in its appli-
cation of Chakrabarty, it is undisputed that, unlike the
claims in Funk Brothers, the claimed composition here has
“the potential for significant utility.” Chakrabarty,
447 U.S. at 310. It is undisputed (and touted in the speci-
fication) that, unlike isolated AAV rh.10 sequences and
non-AAV sequences on their own, various embodiments of
the claimed compositions “are beneficial for gene delivery
to selected host cells and gene therapy patients.” ’617 pa-
tent col. 25 ll. 58–62. This is in stark contrast to the claims
in Funk Brothers, which as the Supreme Court explained,
recited a composition of matter that functioned no differ-
ently whether packaging the individual components to-
gether or separately.
Related to this final point, the parties dispute whether
unclaimed functional distinctions between the claimed
composition and a naturally occurring cell can be consid-
ered as part of the Chakrabarty inquiry. The answer to
this question is found in Chakrabarty itself. As noted
above, the Supreme Court in Chakrabarty emphasized that
no naturally occurring bacteria possessed the same prop-
erty for breaking down crude oil even though the claims
only recited the hydrocarbon-degrading properties of the
plasmids contained by the bacterium rather than any
between the technology at issue here versus Funk Brothers.
The district court differentiated the claimed host cells from
the eligible claim 20 in AMP, reasoning that we concluded
in AMP “that the inventor had altered ‘a cell to include a
foreign gene, resulting in a man-made, transformed cell
with enhanced function and utility.’” REGENXBIO,
2024 WL 68278, at *5 n.3 (quoting AMP, 689 F.3d at 1335–
37). But altering a cell to include foreign sequences via a
laboratory-initiated process, and thus creating something
man-made, is also what occurs to create the claimed host
cells here.
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REGENXBIO INC. v. SAREPTA THERAPEUTICS, INC. 17
capability of the bacterium itself. See 447 U.S. at 305. And
the court nonetheless held that, because “the patentee
ha[d] produced a new bacterium with markedly different
characteristics from any found in nature and one having
the potential for significant utility,” the claims were eligi-
ble. Id. at 310. Accordingly, the court may consider
whether the claimed composition has “the potential for sig-
nificant utility” even if that utility is only implicit—as it
clearly is here.
Sarepta cites ChromaDex to support its view to the con-
trary. But ChromaDex does not undermine Chakrabarty.
The claims in ChromaDex expressly required the composi-
tion to “increase[] NAD+ biosynthesis.” ChromaDex,
59 F.4th at 1283. In other words, the claims defined the
structure of the composition not just by the identity of its
components but also by the overall function of the recited
composition. As such, in assessing whether the claims pos-
sess markedly different characteristics compared to the
natural product(s), this court had to consider this claim
limitation. On the other hand, in Myriad, the Supreme
Court did not analyze function in considering whether the
cDNA claims were markedly different from naturally oc-
curring DNA, as the claims did not recite such a function.
Instead, the Court only analyzed the recited structural dif-
ferences between naturally occurring DNA and the claimed
cDNA. Here, based on our holding above that the claimed
host cells contain molecules that are markedly different
from anything naturally occurring, we need not reach the
question whether they are markedly different based on un-
claimed functions. But even when considering that ques-
tion, Chakrabarty supports holding the claims eligible.
Sarepta further seeks to analogize this case to the inel-
igible claims in Myriad. In doing so, Sarepta does not chal-
lenge that the claimed host cells do not and cannot occur in
nature. Instead, Sarepta seeks to reframe the claims as
directed only to isolating the AAV rh.10 sequence. But the
claim language clearly belies this attempt. Claim 1
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REGENXBIO INC. v. SAREPTA THERAPEUTICS, INC. 18
requires a cultured host cell, a heterologous nucleic acid se-
quence, and a recombinant nucleic acid molecule that codes
for both the heterologous sequence and the AAV rh.10 se-
quence. Because the claims are not simply directed to iso-
lating a newly discovered nucleic acid sequence, we are not
persuaded that the claims here are analogous to ineligible
claims in Myriad.
Sarepta nonetheless urges us to set aside the claims as
a whole and instead focus on isolating the AAV rh.10 se-
quence alone because the other claim limitations are con-
ventional and would not themselves be patentable
advancements. We are not persuaded. Controlling prece-
dent does not direct us to disregard conventional limita-
tions when considering whether claims are “markedly
different” from products of nature. See, e.g., Chakrabarty,
447 U.S. at 310; Diamond v. Diehr, 450 U.S. 175, 188
(1981) (“[I]t [is] inappropriate to dissect the claims into old
and new elements and then to ignore the presence of the
old elements in the [§ 101] analysis.”). We decline to read
out or ignore limitations in a claim merely because they
may be found in the prior art or within the knowledge of a
skilled artisan.6
Accordingly, the claimed host cells here contain a re-
combinant nucleic acid molecule that, by definition, is
markedly different from anything occurring in nature. The
claimed host cells are, therefore, not patent-ineligible
claims to naturally occurring subject matter. Like in Chro-
maDex, our inquiry could end here. However, if resort to
6 While this may prove material for other inquiries
into the validity of the ’617 patent, we emphasize that “par-
ties and tribunals [should] not . . . conflate the separate
novelty and obviousness inquiries under 35 U.S.C. §§ 102
and 103, respectively, with the step one inquiry under
§ 101.” PowerBlock Holdings, Inc. v. iFit, Inc., 146 F.4th
1366, 1373 n.3 (Fed. Cir. 2025).
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REGENXBIO INC. v. SAREPTA THERAPEUTICS, INC. 19
the Alice/Mayo framework is necessary, then at step one we
conclude the asserted claims are not directed to a product
of nature for the reasons stated above. Because we deter-
mine that the claims are not directed to ineligible naturally
occurring subject matter at step one, we do not consider
step two. See CardioNet, LLC v. InfoBionic, Inc., 955 F.3d
1358, 1368 (Fed. Cir. 2020) (“If the claims are not directed
to a patent-ineligible concept under Alice step [one], ‘the
claims satisfy § 101 and we need not proceed to the second
step.’” (quoting Data Engine Techs. LLC v. Google LLC,
906 F.3d 999, 1007 (Fed. Cir. 2018))).
CONCLUSION
We have considered Sarepta’s remaining arguments
and find them unpersuasive. For the foregoing reasons, we
reverse the district court’s summary judgment of ineligibil-
ity under 35 U.S.C. § 101 and remand for further proceed-
ings consistent with this opinion.
REVERSED AND REMANDED
COSTS
Costs to Appellants.
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