By Kevin E. Noonan —
Biotechnology patent law faces the consequences of two decisions handed down last week by the Federal Circuit: In re Kubin and Ariad Pharmaceuticals, Inc. v. Eli Lilly and Co. The first of these illustrates the folly of ignoring the wisdom of the In re Deuel decision, in applying established principles of chemical patent practice to avoid the philosophical error of finding a chemical compound obvious because methods for making an unpredictable compound were well known. The second decision, on the other hand, reflects Judge Lourie's wisdom in recognizing that biotechnology was sufficiently complex that permitting applicants to obtain patents without requiring sufficient disclosure was equal folly, particularly when the technology was developing so rapidly that what an applicant could enable might outstrip what the applicant could describe. While the Ariad Court reaffirmed this principle, Judge Linn's concurring opinion — disagreeing that a written description requirement exists independently of the enablement requirement — suggests that the Court may be forgetting (or choosing to ignore) the wisdom of making sure an applicant's reach does not exceed his or her grasp.
The Kubin decision was based on a misreading of both the Deuel decision and the Supreme Court's decision in KSR International Co. v. Teleflex Inc. The situation in Deuel is well known but bears repeating. The claims at issue were directed to specific nucleic acids encoding human (and bovine) heparin–binding growth factors. The prior art consisted of a reference to certain brain proteins, disclosing partial amino acid sequence, and the Sambrook cloning manual. The U.S. Patent and Trademark Office Board of Patent Appeals and Interferences affirmed rejection on obviousness grounds. The Federal Circuit reversed, based on the absence of any structure in the prior art that could be used to support a finding that the claimed cDNAs would have been obvious to one having ordinary skill in the art. As said clearly in Judge Lourie's opinion:
We today reaffirm the principle, stated in Bell, that the existence of a general method of isolating cDNA or DNA molecules is essentially irrelevant to the question whether the specific molecules themselves would have been obvious, in the absence of other prior art that suggests the claimed DNAs. . . . There must, however, still be prior art that suggests the claimed compound in order for a prima facie case of obviousness to be made out; as we have already indicated, that prior art was lacking here with respect to claims 5 and 7. Thus, even if, as the examiner stated, the existence of general cloning techniques, coupled with knowledge of a protein's structure, might have provided motivation to prepare a cDNA or made it obvious to prepare a cDNA, that does not necessarily make obvious a particular claimed cDNA. "Obvious to try" has long been held not to constitute obviousness. In re O'Farrell, 853 F.2d 894, 903, 7 USPQ2d 1673, 1680-81 (Fed. Cir. 1988). A general incentive does not make obvious a particular result, nor does the existence of techniques by which those efforts can be carried out. Thus, Maniatis's teachings, even in combination with Bohlen, fail to suggest the claimed invention.
The Bell reference, mentioned in the Deuel opinion, disclosed a cDNA sequence for proteins (insulin-like growth factors) wherein the prior art disclosed the complete amino acid sequence. Bell's claims were limited to the exact nucleotide sequence of the human cDNA, and the Federal Circuit's basis for reversing an obviousness rejection by the Board was that this sequence was but one of 1036 possible nucleotide sequences that could encode these human proteins. The cited routine methods for cloning could not have predicted this sequence, out of the 1036 possible nucleotide sequences, as being the one that encoded the human gene.
The Deuel opinion reaffirmed this principle on structural non-obviousness grounds, and extended it to encompass claims reciting the nucleotide sequence in terms of the amino acid sequence it encoded. Judge Lourie, noting that these "genus" claims had not been argued separately, raised but did not address the sufficiency of disclosure issue these claims posed:
Although focusing on the enablement requirement in this passage, in the event (Regents of California v. Eli Lilly) Judge Lourie (at left) focused the inquiry on the written description requirement (ably assisted by a cogent District Court decision by Judge S. Hugh Dillin). The beauty of this line of reasoning was that it was completely consistent with prior Federal Circuit case law on the topic of sufficiency of disclosure for nucleic acid claims. These include Amgen Inc. v. C
hugai Pharmaceutical Co., which first articulated the principle that isolated genes should be considered in patent law like other chemical compounds ("A gene is a chemical compound, albeit a complex one, and it is well established in our law that conception of a chemical compound requires that the inventor be able to define it so as to distinguish it from other materials, and to describe how to obtain it," citing Oka v. Youssefyeh, 849 F.2d 581, 583, 7 U.S.P.Q.2d (BNA) 1169, 1171 (Fed. Cir. 1988)), and Fiers v. Revel ("An adequate written description of a DNA requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it; what is required is a description of the DNA itself. . . . A bare reference to a DNA with a statement that it can be obtained by reverse transcription is not a description; it does not indicate that Revel was in possession of the DNA.").
In Eli Lilly, Judge Lourie set forth a bright-line rule of disclosure:
In claims involving chemical materials, generic formulae usually indicate with specificity what the generic claims encompass. One skilled in the art can distinguish such a formula from others and can identify many of the species that the claims encompass. Accordingly, such a formula is normally an adequate description of the claimed genus. In claims to genetic material, however, a generic statement such as "vertebrate insulin cDNA" or "mammalian insulin cDNA," without more, is not an adequate written description of the genus because it does not distinguish the claimed genus from others, except by function. It does not specifically define any of the genes that fall within its definition. It does not define any structural features commonly possessed by members of the genus that distinguish them from others. One skilled in the art therefore cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the genus. A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is. See Fiers, 984 F.2d at 1169-71, 24 U.S.P.Q.2d (BNA) at 1605-06 (discussing Amgen). It is only a definition of a useful result rather than a definition of what achieves that result. Many such genes may achieve that result. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 U.S.P.Q. (BNA) 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). Accordingly, naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.
Tempered with the possibility that in the appropriate circumstances something other that a nucleotide sequence would satisfy the requirement:
The benefit of this analysis is that it avoids the question of enablement, since a disclosure of one mammalian species ortholog may enable production of others (indeed, this first isolation may be the Rubicon across which all mammalian orthologs are easily obtained, wherein the art did not describe or enable any species prior to its isolation), but without actually obtaining and disclosing it, an applicant is foreclosed from claiming it.
While occasionally losing its way (as in Enzo v. Genprobe I), the calculus developed by Judge Lourie has produced a fruitful equipoise between obviousness and written description for gene patenting over the past decade and a half. On the one hand, the Court's application of the written description requirement ensured that applicants claiming a gene or nucleic acid must be in possession of the molecule. Indeed, the U.S. Patent and Trademark Office has promulgated Written Description Guidelines (on January 6, 2001) and revised Training Materials (on March 25, 2009) specifically addressing the scope of disclosure required to support a nucleic acid claim. This has restricted the scope of these claims to limit them, for example, to encoding the disclosed amino acid sequence and not to encompass substitutions (even conservative ones), insertions, or deletions while permitting fusion proteins in some instances. This approach was approved sub silentio in Kubin, where the Court, despite evident interest at oral argument, chose not to rule on how the Office was applying these rules.
On the other hand, Deuel permitted genes that were not disclosed in the art to be patented without obviousness objections. There is certainly a limit where what is known in the art can, asymptotically, approach obviousness, even in the absence of any known nucleic acid sequence. This is illustrated by In re Bell, where the art disclosed the complete amino acid sequence and thus the claims were limited to a single disclosed nucleic acid species, based on the lack of disclosure in the art as to which of the 1036 possible molecules actually encoded the human gene species. And as the art develops, it becomes more and more routine to obtain cDNA species, impacting the scope of the gene claims that are non-obvious.
This disruption of Judge Lourie's careful balance in Kubin (and the threat Judge Linn's Ariad concurrence raises to written description as a separate requirement) raises again issues of disproportionate application of patent law to certain patentable subject matter, i.e., DNA. It is certainly the case that the progress is not promoted by granting claims of broad scope to disclosures not commensurate therewith. But biotechnology provides something no other technology can: the capacity to produce useful quantities of proteins that form, in many instances, biologic drugs or the means to obtain them. We can, of course, promote a policy where developing these drugs and technologies becomes more difficult and attracts less investment. The question that immediately comes to mind is, why would we want to do that?
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