On 3rd April 2009 the Federal Circuit released two important decisions concerning the patentability of biotechnology claims: one concerning written description and the other concerning obviousness.

In Ariad Pharmaceuticals, Inc v Eli Lilly and Co the Federal Circuit reversed a judgment in favour of Ariad Pharmaceuticals and its licensors MIT, the Whitehead Institute and Harvard University, holding that the patent claims asserted against Eli Lilly for its drugs Evista and Xigris were invalid for lack of written description. The decision applied existing precedent concerning written description in biotechnology and pharmaceuticals, such as the University of Rochester Case. However, a concurring opinion questioned the existence of a written description requirement separate from enablement in determining patentability, showing that the court’s existing precedent in this area is not without controversy among its members.

In re Kubin concerned the patentability of nucleic acid sequences coding for known proteins,and essentially overruled the precedent in this area that had developed from In re Deuel in 1995, holding that the Supreme Court's KSR decision in 2007 made untenable the Federal Circuit’s previous application of the 'obvious to try' concept to conclude that prior art knowledge of a protein and a cloning method did not necessarily render obvious the nucleic acid sequences coding for that protein.

Ariad v Eli Lilly: the written description requirement in biotechnology
Ariad’s patent, which issued in June 2002 as US Patent 6,410,516, was based on the discovery of transcription factor NF-kB and the realisation that the reduction of NF-kB activity could ameliorate the effects of certain diseases, such as those associated with production of cytokines.

After a 14-day trial the jury found that two claims of the patent had been infringed by Evista and two claims had been infringed by Xigris. Claim 95, rewritten in independent form, was exemplary:

"A method for reducing, in eukaryotic cells, the level of expression of genes which are activated by extracellular influences which induce NF-kB-mediated intracellular signaling, the method comprising reducing NF-kB activity in the cells such that expression of said gene is reduced, carried out on human cells. "

As can be seen, the claim did not specify which compounds were to be used in practice of the claimed method. On this basis, Ariad sought to distinguish the University of Rochester Case in which the Federal Circuit held invalid for lack of written description claims drawn to methods of selectively inhibiting COX-2 by administration of unspecified non-steroidal compounds which achieved that result (University of Rochester v GD Searle & Co, 358 F 3d 916 (Fed Cir 2004)).

According to Ariad, the lack of any compound being recited in its claims relieved it of the obligation to describe compounds necessary to practice the method. The court rejected this argument, holding that the specification was still deficient in that its failure to describe the compounds meant that it did not describe practice of the claimed method.

The Federal Circuit went on to explain what it found lacking in the specification, which hypothesised three classes of compound potentially capable of reducing NF-kB activity without giving specific examples. As to each of these three classes, the court noted as follows: 

  • Specific inhibitors - the specification gave one example, which was a naturally occurring peptide. However, the DNA sequence for this substance was not in the original application, but added later. 
  • Dominantly interfering molecules - the specification provided no examples and stated that these compounds would only work “if the DNA-binding domain and the DNA polymerase domain of NF-kB are spatially distinct in the molecule” without stating that these domains actually were distinct. 
  • Decoy molecules - the specification provided several example structures, but did not describe how to use the molecules to reduce NF-kB activity. The court declined to accept the specification’s prophetic example as sufficient description, characterising it as “not so much an ‘example’ as it is a mere mention of a desired outcome”. The decision did not hold that prophetic examples can never provide sufficient written description, but held that the ones here were insufficient.

Accordingly, the court reversed the judgment entered on the jury verdict and held the asserted claims invalid.

In a concurring opinion, Judge Linn joined the panel opinion as supported by existing Federal Circuit precedent, but reiterated his previously expressed disagreement with that precedent. On several occasions in earlier cases, Judge Linn and other members of the Federal Circuit had written that the written description requirement - as applied to hold claims invalid - does not exist as a requirement of patentability that is separate from the enablement requirement. For example, in Enzo Biochem, Inc v Gen-Probe Inc (323 F 3d 956 (Fed Cir 2002)) three judges expressed this view in dissenting from the denial of rehearing en banc, and a fourth wrote that consideration of the matter en banc was not warranted at the time (given the procedural posture of the case), but that it might be in the future.

Judge Linn’s concurrence in the Ariad Case suggests that the previously aired disagreement among members of the Federal Circuit as to the existence of a separate written description requirement still remains.

In re Kubin: obviousness of polynucleotide sequences coding for a known protein
On the same day as the Ariad decision, the Federal Circuit also decided In re Kubin, which came to the court on appeal from the US Patent and Trademark Office (USPTO) Board of Patent Appeals and Interferences. The primary issue in Kubin was the patentability of DNA sequences coding for a known protein when the amino acid sequence of that protein, although not published, could be determined by standard techniques. Because the Federal Circuit affirmed the board’s decision that the claims were unpatentable as obvious, it did not reach the board’s further determination that they also lacked written description.

A representative claim is reproduced below:

"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. "

According to the board's findings, the prior art disclosed: 

  • the existence and function of a polypeptide with an amino acid sequence encoded by the claimed nucleic acid (but not the amino acid sequence of that polypeptide); 
  • a monoclonal antibody to the polypeptide; 
  • a method to determine the polypeptide’s amino acid sequence; and 
  • techniques for synthesising a polynucleotide that would encode that amino acid sequence.

The Federal Circuit affirmed the USPTO’s determination that the claims were unpatentable as obvious over the prior art. The court held that the record supported the USPTO’s factual determination that a person of ordinary skill in the art would have been motivated by the prior art to make DNA encoding the protein at issue given the prior art’s teaching that the protein played a role in the immune response. It also accepted the USPTO’s finding that such a person would have had a reasonable expectation of success given the prior art’s teaching of how to use a monoclonal antibody specific to a protein to clone the corresponding gene. The court did not accept Kubin’s argument that the prior art did not teach the claim’s requirement that the “polypeptide binds CD48”, noting that this property is “necessarily present” in a polypeptide having the claimed sequence.

In affirming the USPTO’s determination that the claimed nucleic acid sequences were obvious in light of prior-art knowledge of the protein, Kubin effectively overruled, at least in part, the holding of In re Deuel (51 F 3d 1552, 1559 (Fed Cir 1995)) that claims to a genus of polynucleotide sequences coding for a known protein are not necessarily obvious. In Deuel the court reasoned that:

‘[o]bvious to try’ has long been held not to constitute obviousness. A general incentive does not make obvious a particular result, nor does the existence of techniques by which those efforts can be carried out.” (Id at 1559.)

More recently, however, the Supreme Court held in KSR that the Federal Circuit’s “obvious to try” jurisprudence was part of an overly rigid approach to obviousness that failed to recognise the creativity and motivation of even those possessing just ordinary skill in the relevant art (KSR Int’l Co v Teleflex, Inc, 550 US 398, 420-21 (2007)). In light of KSR, the Federal Circuit held that the result in Deuel did not control the outcome of this case.
The court also rejected any distinction between allegedly predictable and unpredictable fields of endeavour with respect to judging obviousness under KSR, noting that in this case one of skill in the “advanced art” of biotechnology would find the claimed results “profoundly predictable".

As the court affirmed the board’s decision that the claims were unpatentable as obvious, it did not reach the board’s determination that the claims were also unpatentable for lack of written description. As noted above, however, the court reiterated its recent precedent concerning written description in the field of biotechnology in the Ariad decision issued the same day.