In Agilent Technologies, Inc. v. Synthego Corp., No. 2023-2186 (Fed. Cir. June 11, 2025), the Federal Circuit affirmed the Patent Trial and Appeal Board’s (PTAB) decisions that invalidated all claims of two CRISPR-related patents owned by Agilent Technologies, Inc. (“Agilent”).
Synthego Corp. (“Synthego”) filed two petitions for inter partes review (IPR) challenging all claims of Agilent’s U.S. Patent No. 10,337,001 (the ’001 patent) and U.S. Patent No. 10,900,034 (the ’034 patent). The ’001 patent and the ’034 patent relate to synthetic CRISPR guide RNAs (gRNAs) with specific chemical modifications intended to improve stability and functionality. The CRISPR-Cas system enables targeted cleavage of DNA at specific sites within the genome. The gRNA and Cas protein assemble into a complex with the gRNA. The gRNA guides the complex to a targeted DNA sequence and binds with the target DNA, and the Cas protein cleaves the DNA at that location.
In the IPRs, the PTAB found all challenged claims of the ‘001 patent and the ‘034 patent to be unpatentable as anticipated and obvious. Synthego’s key prior art reference was Pioneer Hi-Bred International, Inc.’s Int’l Pub. No. WO 2015/026885 A1 (Pioneer Hi-Bred) which discloses modified guide polynucleotides used in CRISPR-Cas systems. Synthego also challenged certain claims as unpatentable for obviousness in view of two additional scientific publications (Threlfall and Deleavey). For anticipation, the PTAB determined that Pioneer Hi-Bred anticipated most claims of the two patents by expressly disclosing the claimed gRNA functionality and the relevant chemical modifications. Also, the PTAB found Pioneer Hi-Bred’s disclosure to be enabling. Further, the PTAB found the remaining dependent claims reciting specific modifications as obvious in view of Pioneer Hi-Bred and Threlfall or Deleavey. Agilent appealed.
On appeal, Agilent raised three issues, arguing that: (1) substantial evidence does not support the PTAB’s finding that Pioneer Hi-Bred expressly discloses the claimed gRNA functionality; (2) even if Pioneer Hi-Bred discloses gRNA functionality, it was not enabling as an anticipatory reference; and (3) substantial evidence does not support the PTAB’s finding that a skilled artisan would reasonably expect PACE (phosphonoacetate) and thioPACE modifications to gRNA in a CRISPR-Cas system to be successful.
The Federal Circuit rejected all three arguments and affirmed the PTAB’s decisions in full. On the first argument regarding anticipation, the Federal Circuit upheld the PTAB’s finding that Pioneer Hi-Bred expressly discloses the claimed gRNA functionality capable of binding Cas protein and targeting DNA sequences. Although Pioneer Hi-Bred also included some non-functional examples, the Court emphasized these examples did not negate other disclosures of functional chemically modified gRNAs.
Turning to enablement, the Federal Circuit found no error in the PTAB’s conclusion that Pioneer Hi-Bred was enabling. The Court explained that the inquiry of whether a prior art reference was enabling, and could thus support anticipation, was separate from whether asserted claims were sufficiently enabling to be valid under 35 U.S.C. §112. In the §112 context, enablement ensures the patentee does not obtain a broader monopoly than the specification teaches, but that is not a concern in the enabling anticipatory prior art context (under §102). An enabling anticipatory prior art reference needs only enable a single embodiment of the claim. The Court distinguished its prior decision in Impax Labs, Inc. v. Aventis Pharms., 545 F.3d 1312, 1316 (Fed. Cir. 2008), where the relevant prior art disclosed hundreds or thousands of compounds, several diseases, and broad and general dosage guidelines without sufficient direction or guidance to prescribe a treatment regimen. In this case, the Federal Circuit noted that Pioneer Hi-Bred exemplifies specific RNA sequences having the recited chemical modifications at the recited locations and teaches that gRNA comprising such may be used in CRISPR-Cas systems.
The Federal Circuit also rejected Agilent’s attempt to analogize to Amgen Inc. v. Sanofi, 598 U.S. 594 (2023). The Court distinguished Amgen, noting Amgen was concerned with whether the asserted claims were sufficiently enabled under §112, not whether a prior-art reference was enabling and could thus support (§102) anticipation. The Court further explained that in Amgen the patent required “painstaking experimentation to see what works,” whereas here substantial evidence showed that a person of ordinary skill in the art (POSITA) could understand all the components of a CRISPR/Cas system, gRNA functionality, the types of chemical modifications used in other systems to reduce RNA degradation, and any modifications disclosed and exemplified in Pioneer Hi-Bred.
Finally, on obviousness, the Federal Circuit found that substantial evidence supported the PTAB’s obviousness determination, explaining that obviousness does not necessarily require all the claimed limitations to be expressly disclosed in the primary prior art reference (Pioneer Hi-Bred) but can take account of the inferences and creative steps that a POSITA would employ. The Court credited the PTAB’s comprehensive analysis explaining why a POSITA would have been motivated to combine Pioneer Hi-Bred with the teachings in Threlfall and Deleavey, including the known benefits of the modifications (increased resistance to degradation, enhanced cellular uptake). Further, the Court agreed that combining Pioneer Hi-Bred with Threlfall or Deleavey would have motivated a skilled artisan to use PACE or thioPACE modifications with a reasonable expectation of success and found that the PTAB’s analysis of reasonable expectation of success was thorough and supported by substantial evidence.
Thus, the Federal Circuit affirmed the PTAB’s determination that all claims of the ’001 patent and the ’034 patent are unpatentable.