Federal Circuit Revives Gene-Therapy Patent Under Section 101

April 23, 2026

Navigating the Section 101 Landscape: REGENXBIO v. Sarepta and Its Implications for Patent Eligibility

Oceania Eshraghi, David McIntosh, Melissa Rones, Joshua Talicska Ropes & Gray LLP + Follow Contact LinkedIn Facebook X ;) Embed

In February 2026, the U.S. Court of Appeals for the Federal Circuit issued a precedential decision in REGENXBIO Inc. v. Sarepta Therapeutics, Inc., reversing a district court ruling that had invalidated a gene-therapy patent under 35 U.S.C. §101 (Section 101). 1 In a unanimous opinion by the three-judge panel, the Federal Circuit reaffirmed that genetically engineered cells containing recombinant molecules are patent-eligible subject matter under Section 101, 2 offering meaningful guidance in an area of law that has been in flux for over a decade. This article examines the REGENXBIO decision within the broader evolution of Section 101 jurisprudence and proposed legislative patent reform—including the Patent Eligibility Restoration Act (PERA), reintroduced in both the Senate and the House in May 2025—and is intended to provide practitioners with both a helpful snapshot of the law of patentability as it stands today and practical implications of the decision for the biotechnology industry and beyond.

Setting the Stage: Patent Eligibility and the Alice/Mayo Framework

Section 101, the statute defining patent-eligible subject matter, provides that “[w]hoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor.” 3 Though the statutory text has remained essentially unchanged for over two centuries, courts have gradually carved out judicial exceptions—including exceptions for laws of nature, natural phenomena, and abstract ideas, which are intended to prevent monopolization of fundamental principles needed for innovation and progress—precluding courts from rendering inventions within such categories patent-eligible.

Prior to 2010, the Federal Circuit tended to construe these judicial exceptions narrowly. As such, Section 101 rarely presented a meaningful barrier to patentability. That landscape, however, shifted dramatically between 2010 and 2014, as a series of Supreme Court decisions, namely Bilski v. Kappos (2010), 4 Mayo Collaborative Services v. Prometheus Laboratories, Inc. (2012), 5 Association for Molecular Pathology v. Myriad Genetics, Inc. (2013), 6 and Alice Corp. v. CLS Bank Int’l (2014), 7 substantially expanded the ambit of judicial exceptions to patentability and ultimately culminated in a significant narrowing of patent-eligible subject matter across industries like software and biotechnology.

The resulting two-step Alice/Mayo framework requires courts to first determine (step one) whether claims are “directed to” a patent ineligible concept (e.g., laws of nature, natural phenomena, and abstract ideas), and if so, to then determine (step two) whether the claims contain an “inventive concept” that transforms the ineligible subject matter by adding something “significantly more.” 8 Notably, this framework has been widely criticized for its inconsistent application, as courts grapple with clearly defining what constitutes an “abstract idea” and demarcating a firm threshold for when a claim is sufficiently “directed to” an ineligible concept to necessitate analysis under step two. 9 Critics have further contended that the step two “inventive concept” inquiry improperly conflates eligibility with novelty and non-obviousness under Sections 102 and 103, obfuscating distinctions that Title 35 of the U.S. Code (the Patent Act) treats as separate inquiries. 10

Against this backdrop, the REGENXBIO decision sharpened the contours of patent eligibility and provided meaningful guidance for patent holders and practitioners navigating the post- Alice landscape.

Case Overview: From the District of Delaware to the Federal Circuit

The patent at issue in REGENXBIO, U.S. Patent No. 10,526,617 (the ’617 Patent), contained claims directed to genetically engineered host cells containing recombinant nucleic acid molecules with adeno-associated virus (AAV) sequences. 11 These recombinant molecules are created by chemically splicing together sequences from two different organisms. 12 REGENXBIO Inc. (REGENXBIO), as an exclusive licensee of the patents covering the AAV vector technology, and The Trustees of the University of Pennsylvania, as the owner of the relevant patents, brought a patent infringement action in the District of Delaware against Sarepta Therapeutics, Inc. (Sarepta), whose alleged infringing product was a gene therapy for Duchenne muscular dystrophy manufactured using AAV variant rh.74 in cultured host cells. 13

In January 2024, Judge Richard G. Andrews granted summary judgment to Sarepta, holding that the asserted claims were directed to natural phenomena and thus ineligible under Section 101. 14 Critically, the district court’s analysis focused on the individual claim components rather than the claimed composition as a whole. The court analogized the claims to the Supreme Court’s decision in Funk Brothers Seed Co. v. Kalo Inoculant Co. (1948), 15 reasoning that “[t]aking ‘two sequences from two different organisms and putting them together’ is no different than taking two strains of bacteria and mixing them together.” 16 The court further concluded at step two of Alice/Mayo that the claims lacked an inventive concept, finding the claimed invention was “made using well-understood, routine, and conventional steps.” 17 The Federal Circuit, however, reversed, holding that the claims are directed to patent-eligible subject matter under Section 101, and remanded for further proceedings. 18

“Markedly Different Characteristics”: The Federal Circuit’s Analytical Framework

The Federal Circuit’s reversal centered on the “markedly different characteristics” test from the Supreme Court’s seminal decision in Diamond v. Chakrabarty (1980), under which a composition is patent-eligible when it has “markedly different characteristics” from anything found in nature and possesses “the potential for significant utility.” 19 Two features of the claimed molecules were central to the Federal Circuit’s analysis. First, they were “recombinant,” meaning they comprised sequences spliced together via human intervention from at least two different species. 20 Second, they were “heterologous,” meaning they originated from a different species than the host cell. 21 The Federal Circuit likened the claimed molecules to the man-made plasmid combining four naturally occurring bacteria in Chakrabarty —although both contain naturally occurring segments of DNA, neither are “nature’s handiwork” nor “a hitherto unknown natural phenomenon,” but rather “a non-naturally occurring manufacture of composition of matter.” 22 Accordingly, because the claimed compositions were “undisputedly human made” and contained molecules that “do not exist in nature,” the Federal Circuit found they were distinguishable from mere products of nature and thus patent eligible. 23

Notably, the Federal Circuit resolved the eligibility inquiry at step one of the Alice/Mayo framework, concluding that the claims are not directed to a product of nature and, consequently, that step two analysis was therefore unnecessary. 24 By reaffirming the Chakrabarty framework, the decision resisted an expansive reading of the natural phenomena exception and provided continuity with longstanding eligibility principles.

Sharpening the Line: Engagement with Controlling Precedent

A notable aspect of the REGENXBIO decision is the Federal Circuit’s careful engagement with controlling precedent on patent eligibility for biological compositions. In particular, it focused on three decisions:

• Funk Brothers. The district court had relied heavily on Funk Brothers to invalidate the ‘617 patent, a case in which the Supreme Court held that a mixed bacterial culture was patent-ineligible because the bacteria “perform in their natural way” and serve “the ends nature originally provided.” 25 The Federal Circuit, however, expressly distinguished the claims at issue in REGENXBIO from the composition in Funk Brothers, finding the district court’s analogy “flawed and inconsistent with the undisputed scientific evidence in the record.” 26 Instead, the Federal Circuit explained that “[g]enetically engineering two nucleic acid sequences from separate species into a single molecule and then transforming a host cell in order to incorporate that new molecule into it ... is materially different from growing more than one naturally occurring bacteria strain in a culture where none of the bacteria undergo any change from their natural state.” 27 The court thus clarified that the key differentiator is whether the combination yields a composition with characteristics that could not exist absent human intervention, not merely whether the starting materials are found in nature.
• Myriad. The Federal Circuit aligned its analysis with Myriad, where the Supreme Court held that isolated naturally occurring BRCA genes were patent-ineligible because Myriad “did not create anything,” 28 while cDNA sequences were patent-eligible because “the lab technician unquestionably creates something new when cDNA is made.” 29 In REGENXBIO, the Federal Circuit found that the recombinant nucleic acid molecules claimed by the patent at issue fell squarely on the patent-eligible side of this line – they were not isolated natural products, but rather new compositions created through deliberate human engineering. Importantly, the Federal Circuit noted that splicing together the claimed recombinant molecule and inserting it into a host cell meant that “the lab technician unquestionably create[d] something new,” directly quoting Myriad ’s reasoning. 30
• ChromaDex. The Federal Circuit also distinguished its own prior decision in ChromaDex, Inc. v. Elysium Health Inc., 31 where the Federal Circuit held that claims to an isolated vitamin combined with other milk elements were patent-ineligible absent any “markedly different” characteristics. 32 Unlike the composition in ChromaDex, where the claimed compositions did not exhibit markedly different characteristics from natural milk, the recombinant host cells at issue in REGENXBIO possessed characteristics that plainly could not exist absent human intervention. 33 Embracing a Whole-Composition Approach

In reaching its decision, the Federal Circuit expressly rejected the district court’s component-by-component analysis, which deemed the overall composition at issue ineligible based on a finding that the individual genetic sequences were natural products. 34 Instead, the Federal Circuit emphasized that Section 101 eligibility requires analyzing the claimed composition as a whole. 35 The court reasoned that this whole-composition approach is consistent with Chakrabarty and Myriad and preserves the critical distinction between genuine products of nature and human-made compositions that incorporate natural elements but possess markedly different characteristics overall. 36 A component-level approach, in contrast, risks rendering many biological compositions patent ineligible merely because they incorporate naturally derived genetic material, potentially driving a significant reduction of patent-eligible subject matter across the life sciences and biotechnology sectors.

A Counterweight to the Narrowing of Patent Eligibility

Notably, the principles articulated in the REGENXBIO decision extend well beyond the specific AAV vector technology at issue in the case. The decision’s reaffirmance of the patent eligibility of engineered biological compositions and its emphasis on whole-composition analysis holds potential to benefit innovators across multiple sectors.

The Road Ahead: Legislative Reform and Lingering Uncertainty

Despite the clarity REGENXBIO provides, the broader Section 101 landscape remains unsettled. Sarepta has filed for rehearing en banc, challenging the panel’s analysis, and the outcome of that petition may further shape the contours of Section 101 jurisprudence. Meanwhile, the Supreme Court has repeatedly declined certiorari on Section 101 cases, and members of the patent community, including practitioners, industry stakeholders, and judges, continue to call for greater legislative clarity on patent eligibility. Bipartisan legislation to clarify Section 101, namely PERA, was reintroduced in both the Senate (S. 1546) and House (H.R. 3152) in May 2025. As currently drafted, PERA would eliminate all judicially created exceptions to patent eligibility and replace them with an express list of narrow statutory exclusions, including unmodified human genes and unmodified natural materials. 37 If enacted, PERA could fundamentally reshape the Section 101 landscape by abrogating the Alice/Mayo framework entirely. Until such legislative reform is enacted, however, decisions like REGENXBIO will continue to shape the boundaries of patent eligibility through case-by-case adjudication.

1. See generally REGENXBIO Inc. et al. v. Sarepta Therapeutics Inc., et al., 167 F.4 th 1206 (2026).
2. Id.
3. 35 U.S.C. §101 (2022).
4. Bilski v. Kappos, 561 U.S. 593 (2010).
5. Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66 (2012).
6. Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576 (2013).
7. Alice Corp. v. CLS Bank Int’l, 573 U.S. 219 (2014).
8. Id. at 217–18.
9. See, e.g., Cong. Rsch. Serv., R45918, Patent-Eligible Subject Matter Reform: Background and Issues for Congress (updated Mar. 31, 2025), https://www.congress.gov/crs-product/R45918; Foley & Lardner LLP, Alice Patent Eligibility Analysis Divergence Before USPTO and District Court, Foley.com (Sept. 2024), https://www.foley.com/insights/publications/2024/09/alice-patent-eligibility-analysis-divergance-before-uspto-and-district-court/; David O. Taylor, Confusing Patent Eligibility, 84 Tenn. L. Rev. 157 (2016), https://tennesseelawreview.org/wp-content/uploads/2017/07/confusing-patent-eligibility.pdf.
10. Cong. Rsch. Serv., R45918, Patent-Eligible Subject Matter Reform: Background and Issues for Congress (updated Mar. 31, 2025), https://www.congress.gov/crs-product/R45918; Paxton M. Lewis, The Conflation of Patent Eligibility and Obviousness: Alice's Substitution of Section 103, 2017 Utah OnLaw: Utah L. Rev. Online Supplement, no. 1, art. 1, https://dc.law.utah.edu/cgi/viewcontent.cgi?article=1000&context=onlaw.
11. REGENXBIO, 167 F.4th at 1208.
12. Id.
13. See generally REGENXBIO Inc. v. Sarepta Therapeutics, Inc., 2024 WL 68278 (2024).
14. Id. at *1.
15. Funk Bros. Seed Co. v. Kalo Inoculant Co., 333 U.S. 127 (1948).
16. REGENXBIO, 167 F.4th at 1210 (citing REGENXBIO, 2024 WL 68278, at *5 (internal citation omitted)).
17. Id. (citing REGENXBIO, 2024 WL 68278, at *6).
18. Id. at 1208.
19. Id. at 1211 (quoting Diamond v. Chakrabarty, 447 U.S. 303, 310 (1980)).
20. REGENXBIO, 167 F.4th at 1213.
21. Id.
22. Id. at 1211 (quoting Diamond v. Chakrabarty, 447 U.S. 309–310 (1980)).
23. Id. at 1209.
24. Id. at 1216.
25. Id. at 1211 (quoting Funk Bros., 333 U.S. at 131).
26. Id. at 1214.
27. Id.
28. Id. at 1211 (quoting Myriad, 569 U.S. at 590–91).
29. Id. (quoting Myriad, 569 U.S. at 594–95).
30. Id. at 1213(quoting Myriad, 569 U.S. at 595).
31. Chromadex, Inc. v. Elysium Health Inc., 59 F.4th 1290 (Fed. Cir. 2023).
32. REGENXBIO, 167 F.4th at 1212 (citing Chromadex, 59 F.4th at 1283–84).
33. Id. at 1214.
34. Id. at 1215.
35. Id.
36. Id. at 1215-16.
37. See David M. McIntosh, Joshua Talicska, Sam Ross & Oceania Eshraghi, Patent Reform in the Pipeline: Implications for Industry, Ropes & Gray LLP (Mar. 2, 2026), https://www.ropesgray.com/en/insights/alerts/2026/03/patent-reform-in-the-pipeline-implications-for-industry. ;) ;) Report ### Related Posts

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