Coping With Kubin

The debate over gene sequence patents is leaving investors lost and confused. These strategies will help them find their way

Before May 2007, determining the nucleic acid sequence of a gene encoding a “known” protein was a patentable discovery. Now, a case called In re Kubin stands to overturn precedent, leaving thousands of gene sequence patents hanging in the balance. 

The invention claimed in the Kubin patent application is an isolated nucleic acid molecule encoding a polypeptide at least 80 percent identical to Natural Killer (NK) Cell Activation Inducing Ligand (NAIL). NAIL is a cell surface marker that modulates NK cells, thereby stimulating or inhibiting an immune response. 

The Case for Kubin
The patent examiner rejected Kubin’s claims as “obvious” under 35 U.S.C. § 103. Legally, obviousness is found if an ordinarily skilled artisan could have been motivated by the teachings of one or more prior art references to develop the claimed invention, using ordinary inferences and creative steps. In other words, an invention is obvious if it uses methods known in the art to achieve an expected result or solve a known problem.

The examiner cited the teachings of two prior art references. The first was asserted to inherently disclose the amino acid sequence of p38, a protein that was later determined to be the same protein as NAIL. This reference stated that p38 cDNA could be isolated by conventional techniques. The second reference was cited as teaching conventional techniques for isolating cDNA. The examiner found that the nucleotide sequence claimed in the Kubin patent was isolated by conventional techniques similar to those described in the cited references. The examiner concluded that an ordinarily skilled artisan could reasonably expect to successfully obtain the cDNA encoding NAIL by using methods known in the art-and the sequence was therefore obvious.

Kubin appealed the examiner’s rejection to the Board of Patent Appeals and Interferences (BPAI) in the case Ex parte Kubin. Kubin cited the Federal Circuit case In re Deuel, which states that knowing a polypeptide sequence does not render obvious the underlying nucleotide sequence. BPAI responded that the state of the art has advanced since Deuel, and that the law has also changed.  In May 2007, the BPAI issued a precedential decision affirming the patent examiner’s rejection.

Kubin appealed again, this time to the Federal Circuit Court of Appeals. The case,

In re Kubin

, is currently pending, with briefs still being filed. The Federal Circuit will have to reconcile the precedent set by

In re Deuel

with the newly “clarified” standard for obviousness set forth in the recent US Supreme Court decision,

KSR v. Teleflex

.

In KSR, the Supreme Court stated that when there is motivation to solve a problem and a finite number of predictable solutions, it is “obvious to try” known methods of doing so. If the known methods lead to the anticipated success, the invention itself is likely to be obvious. The patent in KSR, however, was directed to putting electric switches on automobile pedals. The Federal Circuit has long held that biotechnology is an “unpredictable” art, and that problems in molecular biology do not have predictable solutions. BPAI argued that the art has advanced to the point where isolating the gene sequence for a known protein is predictable, not innovative, bringing Kubin within the realm of KSR.

Innovation Marches On
While Kubin is pending before the Federal Circuit, the legal status of gene sequence claims remains uncertain. It’s also likely that the Federal Circuit decision will be appealed or that the court will rehear the case en banc, prolonging this uncertainty. Innovation marches on, however, and new gene sequence patent applications are being filed. Coping with Kubin will require patent applicants to adapt their prosecution strategies to accommodate a legal standard in flux.

The following adaptation strategies apply to gene sequence patents, as well as other inventions and discoveries in the field of biotechnology:

  • Remain silent about whether the problem solved by the invention was known (at least when the problem was likely to be known). Because it makes a solution seem more important, inventors often describe the problem solved by the invention as being widely known or observed. In a KSR/Kubin regime, this preference must not be indulged.  If possible, the applicant should describe the problem in novel terms, or discuss how an aspect of the problem or the magnitude of the problem was not previously known in the art.  

  • Limit discussion of the prior art in the background section of the patent application.  Many inventors include a review of prior art because they think a side-by-side comparison can pre-empt novelty rejections or differentiate their invention from known devices or methods.  Under a more stringent standard for obviousness, however, showing the examiner prior art risks portraying the invention as the predictable next step in the natural progression of the technology.

  • Disclose as much information as possible about the invention and the preferred embodiments and include all reasonably presentable, informative data. Demonstrating that a large amount of experimentation went into the invention makes the results seem less obvious.  Highlight unexpected results. Data can be included as figures, and experimental design and methods can be included as past-tense “examples.” An advantage of including experimental data is that comprehensive disclosure helps satisfy written description and enablement requirements.   

  • Explain one embodiment of the invention in terms of a function or activity that is not described in the prior art. Although many patent attorneys avoid using “functional” claim language, it may be advantageous to claim the invention in both structural and functional terms.  Doing so can help move the patent through prosecution, especially when a function of the invention may be a point of novelty. 

  • Assume that the patent will one day be litigated, and carry this mindset through development of the application. Do not respond to obviousness rejections by presenting arguments that may undermine the patent after it is issued. The safest response to an obviousness rejection is to argue that the cited art teaches away from the claimed invention. Return the examiner’s attention to any unexpected results that were described in the specification.  Avoid arguing the unpredictability of the art, which can come back to haunt a patentee in litigation. The uncertainty surrounding Kubin makes this strategy especially difficult, but also especially important.  Today’s obviousness standard at the patent office may conflict with tomorrow’s standard in court. 

  • Finally, follow any new developments in obviousness.  Since the Supreme Court’s ruling in KSR, the Federal Circuit has affirmed district court findings of obviousness in more than half of the filed appeals. Only time will tell if this increase continues. 

The applicability of KSR to biotechnology and the final outcome of Kubin have yet to be determined. The patentability standards for gene sequences and related technologies may evolve dramatically over the next few years. In the mean time, use these strategies to push your patents to the head of the pack.

Kristina Caggiano is an associate and registered patent agent in the Philadelphia office of the law firm Duane Morris LLP. In January 2009, she will become a clerk for Judge Sharon Prost of the US Court of Appeals for the Federal Circuit. The author would like to thank Vicki Norton in Duane Morris’ San Diego office for her help in editing the article.