In re Fisher, decided September 7, 2005 by a three-judge panel of the U.S. Court of Appeals for the Federal Circuit, holds that ESTs usually will not be patentable unless the function of the corresponding gene is known or disclosed in the patent application. Otherwise, the patent would amount to no more than a "hunting license" for some "real world" benefit of the ESTs, not a disclosure of a completed invention as required by U.S. patent law.
In reaching this decision, the court placed its stamp of approval on the "Utility Guidelines" used by the U.S. Patent and Trademark Office, and brought into question the validity of patents that were granted before those guidelines were rigorously applied. This decision does not create a sanctuary around ESTs, however. ESTs remain patentable as long as the corresponding gene itself satisfies the utility requirement, and the patentability of EST-related technologies, such as microarrays, remain unquestioned.
ESTs are short nucleotide sequences that correspond to a portion of a cDNA clone. ESTs are typically identified by isolating a cDNA clone and sequencing a subsequence of the nucleotides at one end of one strand of cDNA.
ESTs may be used to probe libraries of cDNA collected from a given tissue sample at a given point in time, to identify the genes that were being expressed in the source tissue when it was collected. That information may be useful to identify genes (and encoded proteins) that are active in a given development stage, a given physiological state, or a given disease state, for example.
The Utility Guidelines
Under U.S. patent law (35 USC 101), an invention must be "useful" in order to be patentable. In 2001, the U.S. Patent and Trademark Office adopted "Utility Guidelines" to help U.S. patent examiners apply the utility requirement to certain inventions, including those directed to nucleotide and amino acid sequences. The Guidelines interpret the governing patent statute as requiring a utility that is "specific," "substantial," and "credible," and apply those criteria to several different examples.
One hypothetical example relates to fragments of full-length genes, i.e., ESTs. In this example, a patent application teaches that the ESTs are useful as a probe to obtain the corresponding full-length genes, which can be used to make the encoded proteins, which can be used to study the (unspecified) cellular mechanisms and activities in which the proteins are involved. Importantly, the example assumes that no other use or activity of the encoded proteins is described.
The Utility Guidelines state that the "probe" utility is not a "specific utility" as required to satisfy the statute. The Guidelines explain that the utility is not particular to the claimed ESTsany DNA fragment of any cDNA can be used as a probe to identify the corresponding full-length gene. The Guidelines also state that the disclosed utility is not "substantial," because the only disclosed utility for the encoded proteins is their use in further research on the proteins themselves. Thus, the application does not teach a "real world" utility, as required by the statute.
The Fisher application was directed to ESTs that correspond to genes expressed in maize pooled leaf tissue at the time of anthesis (flower opening). The application taught that the ESTs could be used in a variety of ways, including (1) as a molecular marker for mapping the maize genome; (2) in microarray techniques to obtain information on gene expression in a tissue sample; (3) as a source of primers for PCR to duplicate the genes; (4) to identify the presence or absence of polymorphisms; (5) to isolate promoters by chromosome walking; (6) to control protein expression and (7) to locate genes of other plants and organisms.
The examiner of Fisher's patent application rejected the EST claims for lack of utility, following the rationale set forth in the Utility Guidelines. The Examiner noted that the suggested uses were applicable to any EST and that there was no known use for the encoded proteins. The Board of Patent Appeals and Interferences affirmed, finding that none of the suggested uses was specific or substantial.
The Federal Circuit upheld the Board decision, agreeing that the statute requires "a specific and substantial" utility. The court interpreted this requirement as meaning that the invention must be useful "in its current form, not that it may prove useful at some future date after further research."
Additionally, the utility must relate to "a well-defined and particular benefit to the public." The court reviewed the Patent Office's Utility Guidelines, and found that they comport with its interpretation of the statute's utility requirement.
Turning to the usefulness of Fisher's ESTs, the court noted Fisher's admission that "the underlying genes have no known functions." Although Fisher argued that should be irrelevant, the court disagreed. The court reasoned that, without knowledge of the corresponding gene's function, the ESTs are "objects upon which scientific research could be performed with no assurance that anything useful will be discovered in the end."
Although Fisher argued that the ESTs were akin to patentable research tools, such as a microscope, the court likened the ESTs to chemical compounds with no known use, which long have been held unpatentable.
The court reviewed each of Fisher's asserted uses, and found them all to be hypothetical. For example, there was no indication that the ESTs could be used to identify a polymorphism, or even that a relevant polymorphism exists. Likewise, there was no indication that the ESTs could be used to identify a corresponding gene in another plant or organism, or that such a corresponding gene exists, or has a useful function.
In sum, the court found that Fisher failed to prove that the ESTs could be successfully used in any of the seven ways suggested. The court also noted that the asserted uses were not specific, because any EST from any gene in the maize genome has the potential to perform any of the suggested uses.
The court concluded that granting Fisher a patent to the ESTs "would amount to a hunting license" because the ESTs were "only tools to be used along the way in the search for a practical utility." Simply put, without knowing the function of the corresponding genes, the ESTs do not provide "an immediate, well-defined, real world benefit to the public" that merits the grant of a patent.
Judge Rader's Dissent
Judge Rader dissented from the majority decision, explaining his view that Fisher's ESTs are useful as research tools for isolating and studying other molecules. Judge Rader criticized the majority opinion for making a "value judgment" that the ESTs would not yield "enough" valuable information, noting that scientific advances often occur in incremental steps.
Judge Rader sympathized with the Patent Office's need for some means to reject inventions that advance science to some extent, but not sufficiently to warrant exclusive patent rights, but objected to the use of the utility requirement to achieve that end.
Impact of Fisher
The Fisher decision should put an end to patents directed to ESTs of genes with no known utility, and may bring into question the validity of EST patents issued before the Utility Guidelines were rigorously applied. However, the decision still leaves room for patents directed to certain ESTs and EST-related technologies. For example, ESTs corresponding to genes of known function should satisfy the utility requirement, and EST-based research tools, such as microarrays, should remain patentable.
It is also possible that ESTs corresponding to genes with unknown function but some identified usefulness could satisfy the utility requirement. For example, if a gene is determined to be associated with a specific condition or disease state, but its function is not yet fully understood, a corresponding EST could be useful to screen for the associated condition or disease state.
Thus, while Fisher refuses to grant a "hunting license" on ESTs where the corresponding genes' function is unknown, Fisher does not create a sanctuary around ESTs, but leaves open the possibility for patent protection of ESTs and EST-related technologies as long as they provide a "real-world" benefit.