By Kevin E. Noonan --
Judge Bryson, the third member of the panel deciding the Association for Molecular Pathology v. U.S. Patent and Trademark Office (the Myriad) case, wrote an opinion concurring-in-part and dissenting-in-part. Judge Bryson concurred in the Court's judgment on all issues except the patent-eligibility of isolated DNA molecules including genomic DNA and DNA fragments; he concurred that cDNA was patent-eligible based on its non-existence in nature; indeed, Judge Bryson's opinion was the only one that noted (in a footnote) that plaintiffs' (and certain amici's) argument that the existence of pseudogenes rendered cDNA to be a "natural product" did not establish that any BRCA pseudogene had the sequence recited in any of Myriad's claims. However, Judge Bryson's analysis of the patent-eligibility is flawed by some misunderstandings about biology and chemistry (including particularly medicinal chemistry), and some conclusions having potentially far-reaching consequences for patent-eligibility of more than DNA, consequences more far-reaching than the purported negative impact on innovation postulated by Judge Bryson in his opinion.
The dissenting opinion goes astray almost immediately, by characterizing the question before the Court "[i]n its simplest form" to be "whether an individual can obtain patent rights to a human gene." "From a common-sense point of view, most observers would answer, 'Of course not. Patents are for inventions. A human gene is not an invention.'" The Court's task, of course, is not to apply its version of "common sense." Moreover, this "common-sensical" approach would limit patent-eligible subject matter to the electrical and mechanical arts. An apt example is lincomycin, the antibiotic produced by the bacteria at issue in In re Bergy. In those halcyon days, the patent-eligibility of the purified antibiotic was not at issue, rather it was whether an isolated and purified culture of the bacteria should be ineligible for patenting because they are alive. The antibiotic, also claimed as isolated and purified, is no less a "product of nature" and, by "common sense" reasoning, not an invention. The same will be true of everything falling within the scope of medicinal chemistry. Later in the dissent Judge Bryson disparages the patent-eligibility of isolated DNA as being analogous to plucking a leaf from a tree (echoing Judge Dyk's assertion in his dissent in Intervet Inc. v. Merial Ltd.). The rationale behind the dichotomy between what is an invention and what is not that results from "common sense" would deny patent-eligibility not only to the leaf but to any beneficial chemical compound contained in the leaf.
Next the opinion insinuates that the named inventors' contribution was insufficient to warrant a patent for the claimed isolated DNA molecules, by citing chromosomal mapping work by Mary-Claire King and the use by the inventors of "known sequencing techniques" to isolate the gene. Anachronistically, the dissent treats gene isolation in 1994 as being routine; the achievement of the Human Genome Project and the sequence information resulting therefrom seems to make it easy to forget how difficult gene isolation once was. In view of the fondness of plaintiffs and many amici (as well as members of the panel) for analogies, consider the following: finding the BRCA gene in view of the technology and knowledge before its isolation is like finding a particular house in Chicago from space (or using Google maps) without knowing the location of the house you are looking for. In this analogy, the U.S. is the human genome, Illinois is chromosome 17, and Chicago is the chromosomal region analogous to the location (17q21) identified by Dr. King. This knowledge, which the dissent calls "an unpatentable fact" in no way leads directly to the isolated DNA claimed by Myriad (this DNA also characterized by the dissent as an "unpatentable fact"; in reality, it is a specific chemical compound neither identified nor isolated before Myriad's inventors cloned and sequenced the gene).
Another mischaracterization (advanced at oral argument by plaintiffs' counsel) was that Myriad's composition of matter claims "effectively preempt any attempt to sequence the BRCA genes, including whole-genome sequencing." The inaccuracy of this interpretation of the claims is that it would only be the case if the claim is interpreted to encompass total genomic DNA, an interpretation that would render the claims unpatentable for lack of novelty (inter alia by Miescher's isolation of nuclein in 1869). But this misapprehension clearly informed Judge Bryson's decision, since he concludes that "a contrary ruling [i.e., that isolated DNA is patent-eligible] is likely to have substantial adverse effects on research and treatment in this important field."
Judge Bryson takes from relevant Supreme Court precedent (like Judge Lourie and Judge Moore, Diamond v. Chakrabarty and Funk Bros. Seed Co. v. Kalo Inoculant Co.) the principles used to reach his conclusion (contrary to his fellow judges) than the isolated DNA claims are not patent-eligible. He draws the line at whether the "product of nature" is "structurally and functionally" the same. This focus leads directly to his conclusion, since the dissent discounts the very same structural and functional differences utilized in the majority and concurring opinion to distinguish Myriad's claimed DNA molecules from their "structure and function" in their natural state. (Of course, it should be recognized that these structural and functional differences are much greater than the differences between an antibiotic as it occurs in nature and in its isolated and purified state.). Relying on one of the analogies advanced by plaintiffs (and further exemplifying the rubric that "bad analogies make bad law"), the dissent concludes that Myriad's isolated DNA molecules are "analogous to the 'new mineral discovered in the earth' or the 'new plant found in the wild'" and thus patent-ineligible, again relying on the (false) invention/non-invention dichotomy. In making this argument, the dissent discounts the differences in chemical structure between DNA as it exists in a chromosome and as it exists isolated in a test tube, citing Linus Pauling for the proposition that "[a] chemical bond is merely a force between two atoms or groups of atoms strong enough 'to make it convenient for the chemist to consider [the aggregate] as an independent molecular species.'" Judge Lourie refuted this proposition in the majority opinion with the reality that "a covalent bond is the defining boundary between one molecule and another" and not merely an abstract concept. Indeed, the dissent posits that "there is no magic to a chemical bond that requires us to recognize a new product when a chemical bond is created or broken," thus refuting hundreds of years of chemical arts devoted to producing "new products" precisely by breaking and forming chemical bonds between molecules. Harkening back to another analogy, the dissent admonishes the majority for not recognizing the patent-eligibility of elemental lithium, which may also be purified from its native salts by breaking covalent bonds. A proper reading of the other opinions reveals the actual basis for the other judges' contrary conclusions: elemental lithium is not DNA, and claims to elemental lithium are not before the Court.
The dissent also asserts that the compositions claims are "not defined by any particular chemical formula." This statement ignores the reality that the chemical formula of the BRCA gene could be set forth as the smaller sequence that illustrated Judge Moore's concurring opinion, but that the convention is to represent the chemical formula of isolated DNA by its sequence. This convention does not mean that the isolated DNA is its sequence, any more than any other chemical formula is the claimed chemical compound. The dissent cites the representation of species of the human BRCA genes as being represented by "gaps denoted 'vvvvvvvvvvvvvvvv,'" and that this results in an "almost incalculably large number of new molecules that could be created by filling in those gaps." Insofar as this argument has any relevance, it is to sufficiency of disclosure under 35 U.S.C. § 112, however; that Myriad may not have claimed its invention to satisfy the substantive provisions of the Patent Act does not address the issue of whether the subject matter is itself patent-eligible (presuming that it is properly claimed). The dissent does recognize the unifying principle required for any isolated DNA molecule to fall within the scope of the claims: that it "codes for the same protein as the naturally occurring BRCA1 gene," thus providing its patentable utility.
The dissent then makes yet another analogy, that "extracting a gene is akin to snapping a leaf from a tree." As Judge Lourie noted in the majority opinion,"[w]ith respect, no one could contemplate that snapping a leaf from a tree would be worthy of a patent, whereas isolating genes to provide useful diagnostic tools and medicines is surely what the patent laws are intended to encourage and protect. Snapping a leaf from a tree is a physical separation, not one creating a new chemical entity." It is only by ignoring every substantive difference between cloning a gene and "snapping a leaf from a tree" that the analogy has any merit. And the distinction drawn by the dissent between prior precedent finding patent-ineligibility for naturally occurring products (In re Merz (ultramarine); In re King (vitamin C); In re Marden (vanadium); Gen. Elec. Co. v. De Forest Radio Co. (tungsten)) and patent-eligibility (Parke-Davis & Co. v. H.K. Mulford Co. (adrenaline); Merck & Co. v. Olin Mathieson Chem. Corp. (vitamin B12)) holds only by ignoring the distinctions between the DNA as it exists in the chromosome and the change in structure and function resulting from its isolation. That the dissent considers these differences to be irrelevant (or at best insufficient) to patent-eligibility is evident in the conclusion of the dissent regarding the isolated DNA claims:
The structural differences between the claimed "isolated" genes and the corresponding portion of the native genes are irrelevant to the claim limitations, to the functioning of the genes, and to their utility in their isolated form. The use to which the genetic material can be put, i.e., determining its sequence in a clinical setting, is not a new use; it is only a consequence of possession. In order to sequence an isolated gene, each gene must function in the same manner in the laboratory as it does in the human body. Indeed, that identity of function in the isolated gene is the key to its value. Moreover, as Judge Moore's concurring opinion explains, Myriad has failed to credibly identify new uses for the isolated BRCA genes as probes or primers. The naturally occurring genetic material thus has not been altered in a way that would matter under the standard set forth in Chakrabarty. For that reason, the isolation of the naturally occurring genetic material does not make the claims to the isolated BRCA genes patent-eligible.
Turning to the other claimed compositions of matter encompassed by Myriad's claims, the dissent agrees that cDNA is patent-eligible at least because it cannot be isolated from nature. However, Judge Bryson again parts company with the panel over claims to oligonucleotide fragments of the BRCA genes. Here, the objection is two-fold: first, some of these fragments comprise a BRCA exon, which is "naturally defined by transcription" and that "small sequences of DNA are repeated throughout the three billions nucleotides of the human genome." The latter objection again sounds in overbreadth rather than patent-eligibility, or perhaps novelty (at least with regard to 35 U.S.C. § 102(f)), on the grounds that "efforts to sequence almost any gene could infringe [Myriad's claims] even though Myriad's specification has contributed nothing to human understanding of other genes." This aspect of the dissent's reasoning is illustrated in its discussion of claim 5 of U.S. Patent No. 5,747,282:
5. An isolated DNA having at least 15 nucleotides of the DNA of claim 1.
which the opinion says "is breathtakingly broad." While acknowledging that the claim would most likely be invalidated on other grounds, its breadth gives rise to a discussion of "the effects of broad patent claims on the biotechnology industry" (although if the intent is to somehow protect biotechnological innovation, no doubt many biotechnology companies would gladly forego the proffered protection). Here, the dissent cites the potential problem of patent thickets, and Professor Eisenberg for the possibility that patents might inhibit commercialization of biotechnology inventions. It is well to remember that Professor Eisenberg was originally concerned with patenting inhibiting basic genetic research, and that there is no evidence of any such inhibition despite numerous attempts to detect it. And while it is certain that patents inhibit commercial exploitation by any entity other than the patentee and its licensees, this is hardly unexpected. As noted by Judge Moore in her concurrence:
The dissent suggests that "this may well be one of those instances in which 'too much patent protection can impede rather than 'promote the Progress of Science and useful Arts.'" Dissent at 15-16 (quoting Lab. Corp. of Am. Holdings v. Metabolite Labs., Inc., 548 U.S. 124, 126 (2006) (Breyer, J., dissenting from dismissal of writ as improvidently granted)). Yet the biotechnology industry is among our most innovative, and isolated gene patents, including the patents in suit, have existed for decades with no evidence of ill effects on innovation. See David E. Adelman & Kathryn L. DeAngelis, Patent Metrics: The Mismeasure of Innovation in the Biotech Patent Debate, 85 Tex. L. Rev. 1677, 1681 (2007) ("The existing empirical studies find few clear signs that the patenting of biotechnology inventions is adversely affecting biomedical innovation."); id. at 1729 (concluding "that overall biotechnology innovation is not being impaired by the growth in patents issued").
Similarly, the dissent raises the analogy of the baseball bat made from wood from a tree, and the distinction with isolating DNA that "man has defined the parts that are to be retained and the parts that are to be discarded." As argued by Judge Moore:
The dissent explains why the baseball bat is directed to patent eligible subject matter: "man has defined the parts that are to be retained and the parts that are to be discarded. The result of the process of selection is a product with a function that is entirely different from that of the raw material from which it was obtained." Dissent at 10. The exact same thing is true with regard to primer and probe claims. Man has whittled the chromosomal DNA molecule down to a 15 nucleotide sequence -- defining the parts to be retained and discarded. And the result is a product with a function (primer or probe) that is entirely different from the full gene from which it was obtained.3
3 The dissent analogizes the full BRCA gene to a slab of marble found in the earth as distinct from the sculpture carved into it, which the dissent indicates would be worthy of intellectual property protection. If the multi-thousand nucleotide BRCA gene is the slab, isn't the 15 nucleotide primer the sculpture?
Finally, the dissent rejects the stare decisis principles espoused by the majority and concurring opinions, on the grounds that the Court is not bound by Patent Office policy determinations and that the government's position "substantially undermine[s]" this position. Judge Moore addresses this argument as well:
Changing course years after the fact will only serve to punish those companies who made the reasonable decision to invest large amounts of time and money into the identification, isolation, and characterization of genes. Unsettling the expectations of the biotechnology industry now, based on nothing more than unsupported supposition, strikes me as far more likely to impede the progress of science and useful arts than advance it. Given the complicated technology and conflicting incentives at issue here, any change must come from Congress. See Gottschalk v. Benson, 409 U.S. 63, 72-73 (1972) (A section 101 analysis raises "considerable problems ... which only committees of Congress can manage, for broad powers of investigation are needed, including hearings which canvass the wide variety of views which those operating in this field entertain. The technological problems tendered [by the parties] . . . indicate to us that considered action by the Congress is needed.")
Association for Molecular Pathology v. U.S. Patent and Trademark Office (Fed. Cir. 2011)
Panel: Circuit Judges Lourie, Bryson, and Moore
Opinion for the court by Circuit Judge Lourie; opinion concurring in part by Circuit Judge Moore; opinion concurring in part and dissenting in part by Circuit Judge Bryson