## Facts

- Inventors sought patent claims to a genus of 5‑nitrobenzo[de]isoquinoline‑1,3‑dione derivatives described structurally and asserted “for use as antitumor substances.”
- The specification distinguished the compounds from prior benzo[de]isoquinoline‑1,3‑diones based on non‑symmetrical substitutions at the 5‑ and 8‑positions.
- A prior publication discussed evaluation of related compounds and referenced antitumor screening in two widely used in vivo murine leukemia models (P388 and L1210).
- To address patentability disputes, applicants submitted a declaration reporting in vivo antitumor activity of the claimed compounds in the same murine models and comparative superiority over a prior‑art compound.
- The examiner rejected claims 10–13 under 35 U.S.C. § 112 ¶ 1, asserting the application lacked utility because it did not identify a specific human disease use and did not provide human clinical evidence, and further asserting excessive experimentation would be required for practical use.
- The Board of Patent Appeals and Interferences affirmed, reasoning the evidence did not show “practical” real‑world utility and implying human clinical testing would be necessary.
- Applicants appealed to the Federal Circuit.

## Issues

1. Whether the PTO could sustain a § 112 ¶ 1 utility rejection when applicants provided in vivo murine antitumor data and supporting scientific context, but no human clinical data.
2. Whether the Board properly found lack of enablement under § 112 ¶ 1 based on asserted further experimentation needed to reach practical human therapy.

## Decision

- The Federal Circuit reversed the Board.
- The court held the applicants’ in vivo murine antitumor data, in accepted screening models, sufficiently supported the asserted antitumor utility.
- The court rejected any rule requiring human clinical trials to establish patentable utility.
- The court found the record did not support a conclusion that undue experimentation would be required to make and use the claimed compounds as taught.

## Legal Principles

- Utility under § 101 and the “how to use” aspect of enablement under § 112 are closely linked; the disclosure must teach a credible, well-defined utility and how to practice it.
- Only a reasonable scientific correlation between observed activity and asserted utility is required; utility need not be proven in humans.
- The PTO must provide evidence or sound scientific reasoning to substantiate doubt about asserted utility; it may not reject based on speculation or generalized skepticism.
- Accepted preclinical testing, including established animal models, can provide sufficient evidence of specific and substantial utility when reasonably predictive of the claimed use.
- Enablement is not negated because additional work (e.g., optimization, toxicity testing, clinical trials) would be needed for commercialization; the question is whether the experimentation required to practice the claimed use is undue.

## Conclusion

The Federal Circuit held that credible preclinical antitumor results in widely accepted animal models can satisfy utility and enablement, and that the PTO cannot demand human clinical proof or disregard applicant evidence without a factual, scientifically grounded basis.


In re Brana, 51 F.3d 1560 (Fed. Cir. 1995)