Agilent v. Synthego: Federal Circuit Affirms CRISPR Guide RNA Patents Unpatentable
Agilent Technologies challenged the PTAB’s invalidation of its modified guide RNA patents — central to CRISPR/Cas genome-editing technology — before the Federal Circuit. After 687 days on appeal, the court affirmed all claims of both patents unpatentable, a decisive blow to Agilent’s CRISPR IP position.
Federal Circuit seals Agilent’s CRISPR guide RNA patent losses
Agilent Technologies, Inc. filed appeal No. 23-2186 at the Court of Appeals for the Federal Circuit on 25 July 2023, seeking to overturn a Patent Trial and Appeal Board ruling that all claims of US10337001B2 — and a related patent (the ‘034) — covering modified guide RNAs used in CRISPR/Cas genome-editing systems were unpatentable. The defendant, Synthego Corp., a leading CRISPR genome-engineering company, had successfully challenged those claims before the PTAB in an invalidity/cancellation action on patentability grounds.
The Federal Circuit closed the case on 11 June 2025, affirming the Board’s determination in its entirety. The court expressly considered Agilent’s remaining arguments and found them unpersuasive, leaving all claims of both patents cancelled. For Agilent, affirmance means the patents can no longer be asserted; for Synthego, it confirms freedom to operate in modified guide RNA chemistry without exposure to these specific claims.
The 687-day duration suggests the appeal involved substantive briefing and potentially oral argument, consistent with the complexity of CRISPR patentability disputes. The public record does not reveal whether claim construction, obviousness, or prior art scope drove the Board’s original findings, but the Federal Circuit’s unqualified affirmance suggests no procedural or legal error was identified that could have disturbed the outcome on remand.
Filing to Unpatentable in 687 days
687-day appeal — longer than the median Federal Circuit PTAB review
Federal Circuit affirms: what the PTAB unpatentability ruling means for both parties
Affirmance: the Board’s ruling now stands as final law
When the Federal Circuit affirms a PTAB decision, it concludes that the Board committed no reversible legal error and that substantial evidence supported its factual findings. The court reviewed Agilent’s arguments — likely spanning claim construction, prior art, and obviousness — and found none persuasive. The patents are cancelled; no further administrative route to reinstate the claims exists at this level.
No reversible error foundAgilent loses CRISPR guide RNA exclusivity on all asserted claims
Affirmance extinguishes Agilent’s ability to assert US10337001B2 and the ‘034 patent against any party. Both patents are unpatentable in their entirety — not merely narrowed. Agilent’s CRISPR IP strategy in modified guide RNA chemistry must now rely on other assets, if any exist. The ruling also raises reputational risk for the patent portfolio underpinning any licensing programme Agilent may have pursued in the CRISPR space.
All claims cancelledSynthego’s PTAB victory is cemented — FTO confirmed for guide RNA tech
Synthego now holds a Federal Circuit-affirmed finding that the asserted claims were unpatentable, effectively barring re-assertion of the same claims by Agilent or any subsequent assignee. This outcome is particularly valuable in the competitive CRISPR reagent market, where modified guide RNA synthesis is a core commercial activity. Synthego’s appellate win forecloses the principal patent risk these two patents represented.
FTO confirmed on affirmed groundsCRISPR guide RNA sector: prior art bar for patentability raised
A Federal Circuit affirmance of PTAB unpatentability in the CRISPR space signals that patent claims covering modified guide RNA compositions face rigorous prior art scrutiny. Other portfolio holders with similarly broad claims in this domain should expect heightened IPR challenge risk. For R&D teams developing next-generation guide RNA chemistries, the ruling suggests narrower, more technically specific claiming strategies may be necessary to survive PTAB review.
Heightened IPR risk for guide RNA claimsFull party and counsel information
| Role | Name | Type | Detail |
|---|---|---|---|
| Plaintiff | Agilent Technologies, Inc. | Company | Life-science instrumentation and genomics company — holder of US10337001B2 (CRISPR guide RNA)Search in Eureka ↗ |
| Defendant | Synthego, Corp. | Company | Synthego Corp. — CRISPR genome-engineering company and PTAB petitionerSearch in Eureka ↗ |
| Plaintiff counsel | Aaron Hand | Attorney | Counsel for Agilent Technologies, Inc.Search in Eureka ↗ |
| Plaintiff counsel | Denise Marie De Mory | Attorney | Counsel for Agilent Technologies, Inc.Search in Eureka ↗ |
| Plaintiff counsel | Mark A. Lemley | Attorney | Counsel for Agilent Technologies, Inc.Search in Eureka ↗ |
| Plaintiff counsel | Rebecca Weires Setrakian | Attorney | Counsel for Agilent Technologies, Inc.Search in Eureka ↗ |
| Plaintiff law firm | Bunsow DeMory LLP | Law Firm | Representing Agilent Technologies, Inc.Search in Eureka ↗ |
| Plaintiff law firm | Lex Lumina LLP | Law Firm | Representing Agilent Technologies, Inc.Search in Eureka ↗ |
| Plaintiff law firm | Morrison & Foerster LLP | Law Firm | Representing Agilent Technologies, Inc.Search in Eureka ↗ |
| Defendant counsel | Derek C. Walter | Attorney | Counsel for Synthego, Corp.Search in Eureka ↗ |
| Defendant counsel | Edward R. Reines | Attorney | Counsel for Synthego, Corp.Search in Eureka ↗ |
| Defendant law firm | Jones Day | Law Firm | Representing Synthego, Corp.Search in Eureka ↗ |
| Presiding judge | Judge N/A | Judge | Court of Appeals for the Federal CircuitSearch in Eureka ↗ |
Official order — verbatim text
The Federal Circuit’s affirmance is unambiguous and covers all claims of both patents — not a subset. The phrase ‘find them unpersuasive’ applied to Agilent’s remaining arguments indicates the court conducted substantive review rather than disposing of the appeal on procedural grounds. Under the applicable standard, factual findings from the PTAB are reviewed for substantial evidence and legal conclusions de novo; the court’s affirmance on both patents suggests the Board’s prior art and patentability analysis was well-supported across the full claim sets of US10337001B2 and the ‘034 patent.
US10337001B2 — Modified Guide RNAs for CRISPR/Cas Genome-Editing Systems
US10337001B2 (application number US15/607295) covers modified guide RNAs and their application within clustered, regularly interspaced, short palindromic repeat (CRISPR)/Cas systems — the dominant platform for programmable genome editing. Guide RNAs are the targeting molecules that direct Cas nucleases to specific genomic sequences; chemical modifications to guide RNA backbones or nucleotides can enhance stability, reduce immunogenicity, and improve editing efficiency. The patent sits at the core of a competitive and heavily contested IP domain.
Modified guide RNA technology is commercially critical for every CRISPR therapeutic, agricultural, and research reagent pipeline. Broad claims in this space attract high IPR petition rates because they represent potential blocking positions over entire product categories. The Federal Circuit’s affirmance of unpatentability here is strategically significant: it removes a potential licensing burden for companies synthesising or supplying modified guide RNAs, while signalling to applicants that claims must be technically differentiated from the prior art to survive PTAB review.
Should your R&D team run an FTO against US10337001B2?
Any company developing, manufacturing, or supplying modified guide RNAs — whether for therapeutic, diagnostic, or research use — should note that US10337001B2 has been found unpatentable in its entirety by the Federal Circuit. Products and workflows previously in scope of this patent’s claims are no longer encumbered by it. However, related patents in Agilent’s portfolio, or continuation/divisional applications sharing the same priority chain, may still be active and should be independently reviewed before assuming full freedom to operate.
PatSnap Eureka’s FTO Search Agent allows R&D and IP teams to map guide RNA product designs against all active claims in related patent families — including continuation applications that may not have appeared in prior freedom-to-operate clearances. Eureka surfaces claim-level risk, flags recently filed continuations, and identifies prior art that could support pre-emptive IPR petitions, helping teams move from research to commercialisation with a defensible IP clearance position.
Run a freedom-to-operate analysis on US10337001B2 to assess your product’s exposure
Run FTO in Eureka →Similar CRISPR and guide RNA patent invalidity cases at the Federal Circuit
Cases involving CRISPR/genome-editing patent invalidity appeals at the Federal Circuit, where PTAB unpatentability findings were reviewed on the merits.
What this case signals for the CRISPR IP landscape
A Federal Circuit affirmance in CRISPR patentability is rare and consequential — here is what IP and R&D teams need to act on.
Broad guide RNA claims are vulnerable to IPR challenge at PTAB
The Federal Circuit’s unqualified affirmance confirms that even well-resourced patent holders with sophisticated counsel cannot rescue broad CRISPR guide RNA claims once the PTAB finds them unpatentable. Companies relying on similar claim architectures in their CRISPR portfolios should urgently audit claim scope against published prior art.
Synthego’s win sets a precedent Agilent competitors can cite in future IPRs
An affirmed PTAB unpatentability finding carries persuasive weight in subsequent inter partes review petitions targeting related claims. Competitors and generic manufacturers in the CRISPR reagent space can reference this outcome to strengthen invalidity arguments against overlapping guide RNA patents held by third parties.
Agilent v Synthego — key questions answered
The Federal Circuit affirmed the PTAB’s determination that all claims of Agilent’s US10337001B2 (the ‘001 patent) and its related ‘034 patent — both covering modified guide RNAs for CRISPR/Cas systems — are unpatentable. The court found Agilent’s remaining arguments unpersuasive and issued an affirmance on 11 June 2025, closing the appeal that had been filed on 25 July 2023.
The patents cover modified guide RNAs and their use in CRISPR/Cas genome-editing systems. Guide RNAs direct Cas nucleases to target genomic sequences; chemical modifications can improve stability and editing performance. This technology is foundational to CRISPR-based therapeutics, research reagents, and agricultural applications, making the patent claims commercially significant across multiple industries.
The affirmance means US10337001B2 and the related ‘034 patent can no longer be enforced. Companies developing or supplying modified guide RNA products covered by those now-cancelled claims face no liability under these specific patents. However, related continuations or divisional applications in Agilent’s portfolio may still be active, so independent FTO analysis of the broader patent family remains advisable.
Synthego prevailed at the Patent Trial and Appeal Board in an inter partes review (invalidity/cancellation action) on patentability grounds. The PTAB found all claims of the ‘001 and ‘034 patents unpatentable, and the Federal Circuit affirmed that determination after reviewing Agilent’s appellate arguments. The public record does not specify which prior art references or legal grounds — such as obviousness or written description — were determinative.
Agilent was represented by Aaron Hand, Denise Marie De Mory, Mark A. Lemley, and Rebecca Weires Setrakian, with law firms including Bunsow DeMory LLP, Lex Lumina LLP, and Morrison & Foerster LLP. Synthego was represented by Derek C. Walter and Edward R. Reines of Jones Day. The presence of Mark A. Lemley — a leading patent law academic and litigator — on Agilent’s team underscores the strategic importance of the appeal.
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