By Kevin E. Noonan --
The correspondence between a nucleic acid sequence and its encoded amino acid sequence is the basis for a great deal of how the U.S. Patent and Trademark Office examines biotechnology claims. In many instances the Office treats these sequences differently. For example, it is common practice for the Office to impose a restriction requirement between them, requiring applicants to elect to pursue examination of either nucleic acid claims or protein (amino acid sequence) claims in an application disclosing both. Nucleic acid claims encompassing all of the nucleic acids encoding an amino acid sequence are typically granted, while amino acid sequence variants have become increasingly more difficult to obtain, based in part on the unpredictability of the effects of variants on biological activity.
In the recent non-precedential decision by the Board, Ex parte Chuang, the Office affirmed rejection under 35 U.S.C. § 102(b) of claims to an isolated protein over prior art disclosing a nucleic acid encoding the protein. The rejected claims were directed to the isolated polypeptide:
Claim 20. An isolated polypeptide, comprising a sequence that has at least 95% sequence identity to SEQ ID NO: 1, wherein the polypeptide reduces 15-keto prostaglandin but does not reduce leukotriene B4.
The Office cited three prior art references, directed towards large collections of isolated and sequenced mouse cDNA sequences. These references disclosed the amino acid sequence encoded by the cDNA and identified it as a member of a zinc-containing alcohol dehydrogenase superfamily. The references did not produce the encoded protein nor did they identify the biochemical activity of the protein encoded by the sequence. Nevertheless, the Board affirmed the Examiner's rejection that disclosure in the prior art of a nucleic acid that encodes a protein isolated thereafter anticipates the protein, even if the cited art did not disclose the isolated protein.
The Board distinguished over an earlier Board decision, Lee v. Dryja, 79 U.S.P.Q.2d 1614 (B.P.A.I. 2005), holding that a "cDNA is at most an equivalent of its encoded protein but does not contain every element of the isolated protein encoded thereby." Moreover, the Lee case further held:
[A]ssuming arguendo that it was well within ordinary skill in the art to prepare, isolate and purify the protein product of a given cDNA clone at the time the '163 application [the patent application at issue] was filed, the 4.7 kb cDNA described in the '163 specification would have made its encoded protein obvious at best.
The Board based its reasoning on In re Donohue, 766 F.2d 531 (Fed. Cir. 1985), which held that "[i]t is not, however, necessary that an invention disclosed in a publication shall have actually been made in order to satisfy the enablement requirement." Accordingly, the Board reasoned that the references cited by the examiner provided an enabling disclosure of the protein encoded by the disclosed nucleic acids, and were anticipating. The Board noted that the burden is on applicants to establish that the cited art is not enabling.
Specifically with regard to the Lee case, the Board first noted that Lee was an interference case, and the issue decided therein was whether Dryja had produced sufficient evidence that it had possession of a single enabled embodiment within the scope of the interference count. This standard for interferences differs from the standard for anticipation, said the Board, although here that statement seems in error: the Board would have been in the same position with regard to the cited references if each had only enabled the embodiment identified as SEQ ID NO: 1. Second, the Board noted that Dryja did not disclose a complete coding sequence for the protein at issue in the interference count. In that case, the presence of a translation stop codon in the cDNA prevented Dryja's cDNA from expressing full length protein. None of the references cited against applicants in this case suffered from this infirmity, and it was undisputed that the cDNA could have (but had not) been used to produce the claimed protein.
While non-precedential, this case illustrates that the Office will now consider disclosed nucleic acids to be anticipating references to claims for isolated polypeptides. This attitude has far-reaching implications for biotechnology, in view of the extensive public disclosure and annotation of open reading frames in sequences determined by the Human Genome Project. It also contrasts starkly with the more stringent utility requirement for claiming such sequences, wherein applicants must show possession of not only the isolated nucleic acid and expressed protein thereof but also a specific, substantial, and credible utility for nucleic acids and proteins. Thus, the Office imposes a standard of knowing the function of a protein encoded by a nucleic acid, but considers the mere disclosure of the nucleic acid to anticipate not only the nucleic acid but the protein encoded thereby. Under these circumstances, it is likely that no later-filed claims to proteins encoded by open reading frames identified from the Human Genome Project will be patented, even if the protein has a unique, unappreciated biological activity. This stance by the Office will put to the test the belief by many in the biotechnology community that patent protection is necessary to obtain investment in technologies derived from the explosion of genetic information that even now has not been completely elucidated, and that the absence of patent protection will retard if not preclude such investment. It may be an expensive lesson to learn.