A typical scenario in the development of biotech patents claiming DNA sequences: a bench researcher discovers the isolation and characterization of a protein that may have desirable biological activity and publishes a paper describing the results. A biotech company then clones the cDNA for the described protein, characterizes the cloned sequence and files a patent application for the nucleic acid molecule that encodes the amino acid sequence for the protein. In the past, it would have been expected that the biotech company would be granted a patent on the nucleic acid molecule; however, after the Federal Circuit’s decision in In re Kubin, patents on DNA sequences may be more difficult to obtain, and “obvious to try” rejections may become more frequent.

On April 3, 2009, the Federal Circuit affirmed the Board of Patent Appeals and Interferences (the “Board”) obviousness rejection of the patent claims by Kubin and Goodwin to DNA molecules encoding a protein known as natural killer (NK) cell activation inducing ligand (NAIL). The decision placed significant emphasis on the Supreme Court’s application of the “obvious to try” standard in KSR[1] and overturned the Federal Circuit’s In re Deuel[2] decision.

Of note, the Federal Circuit declined to address the Board’s rejection based on written description. As a result, patent practioners will have to wait and see how the Federal Circuit interprets claims that add a functional limitation to a genus of sequences defined by a percent identity to a single sequence described in the application (i.e., a polypeptide at least 80% identical to SEQ ID NO: 2 and having a specific function).

The claims at issue, represented by claim 73 below, are directed to a genus of isolated polynucleotides encoding a protein that binds CD48 and is at least 80% identical to amino acids 22-221 of SEQ ID NO:2, which is the disclosed amino acid sequence for the CD48-binding region of NAIL.

73. An isolated nucleic acid molecule comprising a polynucleotide encoding a polypeptide at least 80% identical to amino acids 22-221 of SEQ ID NO:2, wherein the polypeptide binds CD48.

The Board rejected the application as obvious over two prior art documents: a patent, Valiante et al.[3], disclosing the existence of a protein, p38, later found to be encoded by the NAIL cDNA invented by Kubin; and Sambrook et al.[4], a cloning manual used to establish what was routine in the art. Despite disclosures in the patent application relating to specific steps required for activation of the NK cells that were not found in either prior art reference, the Board found that “the product [is] not of innovation but of ordinary skill and common sense, leading us to conclude NAIL cDNA is not patentable as it would have been obvious to isolate it.”[5]

The Federal Circuit held that appellants’ methodology of isolating NAIL cDNA was essentially the same as the prior art and “obvious to try,” based on the known properties of these proteins. Emphasizing that it did not matter that the claims were directed to a genus of polynucleotides instead of a method of DNA cloning or isolation as described in the prior art, the Federal circuit said:[6]

The emphasis on similarities or differences in methods of deriving the NAIL DNA misses the main point of this obviousness question. Of note, the record nowhere suggests that the technique in Valiante’s [the prior art] Example 12 for isolating NAIL (p38) DNA, even if slightly different than the technique disclosed in the claimed invention, would not yield the same polynucleotide claimed in claim 73. Stated directly, the record shows repeatedly that Valiante’s Example 12 produces for any person of ordinary skill in this art the claimed polynucleotide.

In the 1995 In re Deuel[7] decision, the Federal Circuit reasoned that methods of isolating a DNA molecule did not provide information on the DNA molecule’s nucleotide sequence and, thus, did not render claims to the sequence obvious. Now, the Federal Circuit is applying KSR as rejecting In re Deuel. [8]

Insofar as Deuel implies the obviousness inquiry cannot consider that the combination of the claim’s constituent elements was “obvious to try,” the Supreme Court in KSR unambiguously discredited that holding. In fact, the Supreme Court expressly invoked Deuel as a source of the discredited “obvious to try” doctrine. The KSR Court reviewed this court’s rejection, based on Deuel, of evidence showing that a particular combination of prior art elements was obvious because it would have been obvious to one of ordinary skill in the art to attempt such a combination.

Thus, it appears that the Federal Circuit has clearly signaled that as technology has advanced, so has the level of what will be considered obvious to one of ordinary skill in the art. If the prior art points to a need to solve a problem and provides good reasons or a method for pursuing the solution, the result may be found obvious. It is clear that the In re Kubin decision will make it harder to obtain claims to DNA sequences encoding a protein when the encoded protein is already known. This decision will also impact issued DNA patents entering the reexamination process or litigation. For patents where an encoded protein was known at the time the application was filed, a patent examiner can now rely on In re Kubin to reject claims based on the known protein and standard cloning techniques. Courts may do the same.