Background
The patent application at issue, filed by Kubin and Goodwin, claimed an isolated DNA sequence encoding the NAIL protein — a receptor expressed on natural killer (NK) immune cells that plays a role in immune activation. NAIL had been identified and characterized at the protein level before the application was filed, including in a prior art disclosure by Valiante and Trinchieri. While the prior art disclosed the NAIL protein and its functional properties, it did not disclose the specific DNA sequence encoding it. Kubin and Goodwin argued that isolating and sequencing the encoding DNA was a novel and patentable contribution — not obvious even if the protein was known.
The PTO Board of Patent Appeals and Interferences rejected the claims as obvious over Valiante (which disclosed the protein) combined with routine cloning techniques, and the applicants appealed, arguing that the Board had improperly applied the pre-KSR TSM test and that KSR’s rationale did not apply to biotechnology sequence claims.
The Court’s Holding
The Federal Circuit affirmed the rejection. The court held that when the prior art discloses a protein and teaches that its encoding DNA can be isolated using known, routine cloning techniques, it is obvious to isolate and claim the encoding DNA sequence. Under KSR’s flexible approach, it is not necessary to find explicit teaching, suggestion, or motivation in the prior art to find a claim obvious — if a skilled worker would have had both the motivation to obtain the DNA sequence (to use it for research or therapeutic purposes) and a reasonable expectation of success using routine methods (PCR-based cloning, probe hybridization), the claim is obvious.
The court distinguished cases where cloning a gene was genuinely uncertain or technically challenging at the time — where success was not reasonably predictable — from cases where routine methods could predictably yield the claimed sequence given knowledge of the protein. In Kubin, the relevant cloning techniques were well-established by the time of filing, and the prior art gave skilled researchers sufficient guidance and motivation to clone NAIL. The claim was therefore obvious.
Key Takeaways
- Under KSR, isolating and claiming a DNA sequence encoding a previously known protein is obvious when the prior art discloses the protein, teaches routine cloning methods, and gives skilled researchers a reason to clone the gene — even without explicit prior art disclosure of the specific sequence.
- Reasonable expectation of success using routine methods is a critical component of the obviousness analysis in biotechnology: if known techniques predictably yield the claimed genetic material, the claim is likely obvious.
- KSR’s flexible approach applies to biotechnology patent claims, including genetic sequence claims — the biotech industry does not have a categorical exception from the heightened post-KSR scrutiny applicable to other technology areas.
- Patents on DNA sequences encoding known proteins should be evaluated carefully for obviousness in view of routine cloning techniques and prior art protein characterization — the mere isolation of a sequence encoding a known protein, using standard methods, is unlikely to be patentable post-KSR.
Why It Matters
In re Kubin was the Federal Circuit’s first major application of KSR’s flexible obviousness standard to biotechnology sequence claims — a significant development given the enormous number of gene patents issued during the 1980s and 1990s when the TSM framework had made such patents easier to obtain and maintain. The decision signaled that the post-KSR environment would impose more rigorous scrutiny on genetic sequence claims based solely on isolation of sequences encoding previously characterized proteins.
The ruling contributed to a broader reassessment of gene patent scope and validity that culminated in Association for Molecular Pathology v. Myriad Genetics (Supreme Court 2013). Together, Kubin (obviousness) and Myriad (§ 101 eligibility) significantly narrowed the patent protection available for genetic sequences, establishing that both doctrines could be used to challenge claims that merely isolated naturally occurring sequences or sequences predictably derived from known proteins using routine techniques.