Navigating Subject Matter Eligibility §101 for Diagnostics in a Changing Patent Landscape

Overview

Subject matter eligibility under 35 U.S.C. § 101 has long been a challenging hurdle for biotech and pharmaceutical innovators. Diagnostic method claims have been especially difficult, with federal courts invalidating virtually every diagnostic assay patent challenged post-Mayo (Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66 (2012)).  But recent USPTO actions signal a meaningful shift in how eligibility is evaluated at the examination stage, creating new opportunities for applicants who act strategically and leverage evolving USPTO guidance.

A recently issued U.S. Patent, U.S. Patent No. 12,419,201, directed to cancer diagnostic methods, illustrates this shift. Since late 2025, our firm has observed this change firsthand. Diagnostic patent applications that previously faced persistent §101 rejections are now either advancing to allowance or no longer receiving eligibility rejections. The following strategies reflect developments in USPTO practice and PTAB review and are designed to help applicants secure and maintain strong, enforceable diagnostic patents.

1. Leverage the August 2025 Kim Memo in Prosecution

On August 4, 2025, USPTO Deputy Commissioner Charles Kim issued guidance reminding examiners that: (i) §101 rejections should be made only when there is a clear basis for concluding that a claim is more likely than not ineligible-mere uncertainty is insufficient; (ii) claims must be evaluated as a whole, rather than isolating individual claim limitations; and (iii) an advantageous technological outcome should be recognized as a technological improvement for eligibility purposes.

Reminding an examiner of this guidance may help to address reflexive or inadequately supported §101 rejections in diagnostic applications. It provides a strong framework for challenging conclusory eligibility rejections in written responses and is useful during examiner interviews involving diagnostic claims.

2. Consider Filing a Subject Matter Eligibility Declaration (SMED)

Consistent with recent USPTO guidance to the Patent Examining Corps, including the April 30, 2026 USPTO memorandum, Subject Matter Eligibility Declarations (“SMEDs”) may be used to present objective evidence specifically directed to the § 101 analysis. A well-prepared SMED acts as a “constructive model” that helps examiners understand real-world technological application, such as diagnostics, where traditional working models are impractical.

A specification need not explicitly set forth an improvement, as long as it describes the invention in a manner from which one skilled in the art would recognize the technical advancement. When such improvements are not explicitly stated in the specification, they may still be addressed during prosecution. When properly prepared and grounded in the specification, SMEDs are most effective when they provide a clear nexus between the claimed invention and the factual assertions in the declaration. For example, a SMED may: (i) establish the state of the art as of the filing date; (ii) explain why the claimed detection steps cannot practically be performed in the human mind; (iii) present objective evidence, such as performance metrics, demonstrating technological improvements over conventional methods; or (iv) clarify how the claimed method provides a concrete and practical clinical application.

The April 30 memo further emphasizes best practices including avoiding supplementation of the specification, and submitting SMEDs as separate Rule 132 declarations, rather than combining them with obviousness and enablement assertions. A well-prepared SMED can help shift the eligibility inquiry in the applicant's favor. One consideration, however, is that the declarant may be subjected to deposition if the patent is later litigated.

3. Understand the Litigation-USPTO Gap

While the USPTO's more favorable examination posture is encouraging, the federal courts are not bound by USPTO guidance. Patents obtained under current USPTO practice may still face heightened invalidity risk in litigation. Diagnostic innovators should work closely with experienced counsel to ensure the claims are defensible under Federal Circuit precedent and not solely under USPTO guidance standards. Until Congress acts or the Supreme Court revisits §101, careful planning in view of the litigation-USPTO gap remains essential.

4. Monitor PTAB Trends and Learn from Successful Appeals

Since Director John A. Squires took office in September 2025, PTAB treatment of §101 issues have shifted noticeably. PTAB decisions issued since October 2025 have shown an increased rate of reversals of examiner eligibility rejections. Many of these reversals provide lessons for how to better combat §101 rejections during prosecution.

For example, in view of Ex Parte Desjardins, Appeal 2024-000567 (PTAB Sept. 26, 2025) a specification that identifies a technical improvement reflected in the claims remains one of the strongest defenses against §101 eligibility rejections. For diagnostic applications, this means articulating how the claimed method improves upon existing detection techniques. For example, does the method enable faster processing, reduce false positives, permit detection at lower analyte concentrations, or integrate previously incompatible assays?

The precedential Desjardins decision makes clear that improvements in system functionality or operational efficiency can constitute patent-eligible technological advances. For diagnostics, this principle may extend to improvements in assay design, detection methodology, or clinical workflow. If your application receives a §101 rejection and you have objective evidence of technical improvements, an appeal to the PTAB may be more favorable now than in prior years.

5. Tie Diagnostic Claims to Specific Clinical Actions

Method of treatment claims continue to fare better than pure diagnostic claims under the Mayo/Alice framework. Cases like Vanda Pharmaceuticals v. West-Ward Pharmaceuticals, 887 F. 3d 1117 (Fed. Cir. 2018) demonstrate that claims integrating a diagnostic finding into a specific therapeutic action have a better chance of satisfying §101. Where appropriate, applicants should structure claims to include actionable clinical steps. For example, administering a specific therapy based on diagnostic results. This transforms a potentially ineligible observation into a patent-eligible treatment method. One important consideration, however, is enforcement. Claims tying diagnostics to treatment actions may raise questions regarding the proper infringement target, such as whether liability lies with the diagnostic company, the treatment provider, or both.

6. Reassess Previously Abandoned Diagnostic Applications

The current examination environment creates a renewed opportunity to revisit diagnostic innovations that were previously on hold. To the extent companies have pending patent families with disclosures directed to diagnostic methods that were previously rejected or on hold due to §101 concerns, companies should contemplate filing a continuing application as they may have a higher chance of success moving forward.

A Call to Action: Secure Patent Protection for True Innovation

At the USPTO level, the §101 landscape for diagnostics is the most favorable that it has been in over a decade. But success requires strategic execution. Applicants that draft specifications emphasizing technical improvements, integrate diagnostics findings with therapeutic actions, and leverage evidentiary tools, such as separately filed SMEDs, are best positioned to secure enforceable patents without sacrificing claim scope. With careful planning and informed prosecution strategies, diagnostic innovations once deemed patent ineligible can now be meaningfully protected.

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Susie Cheng

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