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June 01, 2009 (Vol. 29, No. 11)

Patentability of Genetic Sequences Limited

Federal Circuit Decision Will Affect Obviousness Standard Moving Forward

  • The Kubin Case

    Kubin is a pivotal post-KSR obviousness case addressing the classical biotechnology invention involving the cloning and characterization of a human gene encoding an isolated, but not yet sequenced, protein. The human NAIL protein was known to exist on the surface of natural killer (NK) cells and bind to the CD48 protein to elicit an immune response against certain viruses and tumors.

    Kubin and Goodwin isolated and cloned a human NAIL protein using an available antibody to the murine version of the protein, and a cDNA expression library generated from pooled mRNAs extracted from human NK cells stimulated with known activators. They became the first to sequence both the cDNA and amino acid sequences of such a protein.

    The claims in Kubin are directed to a genus of isolated nucleic acid molecules encompassing an extracellular binding domain of the NAIL protein that binds to CD48. The claims at issue were held invalid as obvious under 35 U.S.C. §103(a), and for lack of enablement and failure to meet the written description requirement under 35 U.S.C. §112, 1st paragraph. The Federal Circuit only discussed the obviousness aspects of the invention. It did not address many issues of fact regarding undefined expression and cloning parameters in the prior art that were necessarily elucidated in order to reveal the cDNA sequence.

    Relying on KSR, Judge Randall R. Rader eliminated the effective nonobviousness presumption that biotechnology has enjoyed as an unpredictable art. In writing for the Federal Circuit, he stated that “this court cannot deem irrelevant the ease and predictability of cloning the gene that codes for that protein. This court cannot, in the face of KSR, cling to formalistic rules for obviousness, customize its legal tests for specific scientific fields in ways that deem entire classes of prior-art teachings irrelevant, or discount the significant abilities of artisans of ordinary skill in an advanced area of art.”

    Rader further stated that KSR limits the Federal Circuit’s reliance on Deuel. “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,” Rader said. Regarding the proper use of the “obvious to try” standard, Rader noted that the Supreme Court’s admonition against such a formalistic approach to obviousness “actually resurrects this court’s own wisdom in” In re O’Farrell, 853 F. 2d 894 (Fed. Cir. 1988).

    O’Farrell acknowledged that the “obvious to try” standard can be erroneously equated with obviousness in two situations. As restated in Kubin, the first situation where an invention might be argued to be “obvious to try”—but the lack of predictability of the result mitigates against obviousness—is “where a defendant merely throws metaphorical darts at a board filled with combinatorial prior-art possibilities.” This was contrasted with KSR obviousness “where a skilled artisan merely pursues ‘known options’ from a ‘finite number of identified, predictable solutions.’”

    The second remaining nonobviousness situation, where “obvious to try” does not mitigate toward ultimate obviousness, is when the “obvious to try” was to explore a new technology or general approach that seemed to be a promising field of experimentation—where the prior art gave only general guidance as to the particular form of the claimed invention or how to achieve it. Kubin indicated that KSR affirmed the inverse of this statement by stating that an invention is obvious unless “the improvement is more than the predictable use of prior-art elements according to their established functions.”

    Rader found that neither of the two “obvious to try pitfalls” applied in Kubin, concluding that “the record shows that a skilled artisan would have had a resoundingly ‘reasonable expectation of success’ in deriving the claimed invention in light of the teachings of the prior art.” The Federal Circuit acknowledged that the invention in Kubin was “some minor advance in the art,” but that “granting patent protection to advances that would occur in the ordinary course without real innovation retards progress.”

  • Kubin's Impact on Gene Patenting

    The Federal Circuit’s decision in Kubin generally means that, to the extent a protein has been previously identified, its nucleotide sequence is no longer patentable. The broader application of Kubin will include attempts to reject or invalidate claims directed to biotech inventions that claim an outcome of experimentation from among a range of expected results, even though not expressly predictable.

    There will undoubtedly be an increase in invalidity challenges to existing gene patents by those seeking to market generic and follow-on biologics prior to patent expiration, in view of the likelihood that pending regulatory legislation also passes. Clearly, the patentability standard for gene sequences and the commercial exclusivity available for such biotech inventions have been dramatically altered by the Federal Circuit’s In re Kubin decision.

Posted 6/17/2009 by q.c.specialist

excellent article!


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