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
Kevin,
Nice "dissection" of Judge Bryson's nonsensical dissenting opinion. Judge Bryson is apparently in Judge Dyk's (see Invert v. Merial) camp on the isolated gene sequence issue. Their views mystify and annoy me from the standpoint of ignoring the science, chemistry, molecular biology, and more significantly, the reality here. You would expect such rhetorical nonsense from a disctrict court judge (e.g., Judge Sweet) or perhaps from the Supreme Court. But not the Federal Circuit.
Posted by: EG | August 04, 2011 at 05:40 AM
Kevin,
Thank you for tackling a topic that most fear to touch with the proverbial ten foot pole: Judicial incompetence in areas (i.e. biochemistry) where they know not how incompetent they truly are.
What to do about it?
This is a big problem because judges yield extraordinary power and oft suffer from hubris as well as self-inflicted blindness due to the brilliance of their own self-adjudged high IQs.
I for one, do not see any simple answers.
Maybe a first step is for all judges to exercise some form of transparent humility by admitting on record that they did not spend 10 years in graduate school earning a PhD in biotechnology and admitting that perhaps there are some areas of knowledge that are not easily acquirable though a 2 minute tutorial from a biased lawyer. If the latter were true (that anything and everything can be learned via 2 minute tutorial), then we are all foolishly wasting billions of dollars by sending our sons and daughters to college and graduate school.
Posted by: step back | August 04, 2011 at 06:04 AM
"Another mischaracterization... The inaccuracy of ..."
- One needs sequencing primers and they potentially fall within the 15-nucleotide claims. So Judge Bryson maybe right for the wrong reason.
Posted by: DSK | August 04, 2011 at 08:36 AM
Dear DSK:
I might agree if I thought the primer claims were valid - but I don't think they are. But not for the reasons Judge Bryson thinks they are not.
Thanks for the comment.
Posted by: Kevin E. Noonan | August 04, 2011 at 01:25 PM
Dear step:
To be fair, part of the blame lies on the lawyers and the judge's clerks for not assiting the court to understand the issues.
But the problem you mention has a solution, one proposed by Learned Hand in the last century:
"The test laid down [in 35 U.S.C. § 103] is indeed misty enough. It directs us to surmise what was the range of ingenuity of a person "having ordinary skill" in an "art" with which we are totally unfamiliar; and we do not see how such a standard can be applied at all except by recourse to the earlier work in the art, and to the general history of the means available at the time. To judge on our own that this or that new assemblage of old factors was, or was not, "obvious" is to substitute our ignorance for the acquaintance with the subject of those who were familiar with it. Reiner v. I. Leon Co., 285 F.2d 501 (2d Cir. 1960)
"Courts, made up of laymen as they must be, are likely either to underrate, or to overrate, the difficulties in making new and profitable discoveries in fields with which they cannot be familiar; and so far as it is available, they had best appraise the originality involved by the circumstance which preceded, attended and succeeded the appearance of the invention. Safety Car Heat & Light Co. v. General Electric Co., 155 F.2d 937 (2d Cir. 1946)."
Thanks for the comment.
Posted by: Kevin E. Noonan | August 04, 2011 at 01:29 PM
"But the problem you mention has a solution, one proposed by Learned Hand in the last century:"
A rather poor solution, and one which gets worse as arts get more and more complex with each passing day.
But never mind all that, gimme that ol' time religion, I say gimme that ol time patent religion!
Posted by: 6 | August 04, 2011 at 02:58 PM
Thanks, Kevin. As Sideshow Bob might say, "Euhhhhhhhhh".
I noticed that Judge Bryson was also on the panel that decided Schering v Geneva. In that case, Judge Rader, writing for the panel, noted near the end of the opinion that although the metabolite claimed in claim 1 had existed before, proper claim drafting could still have saved something for the patentee:
"A skilled patent drafter, however, might fashion a claim to cover the metabolite in a way that avoids anticipation. For example, the metabolite may be claimed in its pure and isolated form, as in Kratz and Bergstrom, or as a pharmaceutical composition (e.g., with a pharmaceutically acceptable carrier). The patent drafter could also claim a method of administering the metabolite or the corresponding pharmaceutical composition. The '233 patent would not provide an enabling disclosure to anticipate such claims because, for instance, the '233 patent does not disclose isolation of DCL."
Judge Bryson didn't dissent then, implicitly agreeing with the statement, but the positions he takes in AMP seem to be at odds with the view in Schering. I wonder if the inconsistency is due to a change of heart, or just sloppiness.
Posted by: Dan Feigelson | August 05, 2011 at 01:18 AM
Dear Dan:
Sometimes it's context; I think he believed Chris Hansen when he said the composition of matter claims would raise infringement liability for whole-genome sequencing.
Thanks for the comment.
Posted by: Kevin E. Noonan | August 05, 2011 at 06:52 AM
Kevin,
You picked on poor Judge Bryson's ignorance re DNA molecules.
But how about Judge Moore?
Isn't she equally guilty (although to a much lesser degree)?
Moore J. "gets it" about the end bonds of the isolated molecule. But does she mention protein folding, enzyme attachment, etc.?
Mind you, I'm no biochemist and therefore I am well out of my normal woods when it comes to this stuff. But I get a sense that the judges involved are even farther out in the open meadow when it comes to scientifically complex issues such as these.
One shudders to think what will happen when stuff like this moves up into the US Supreme Court!
(...and yes, I do recall you have a past history with one of the justices)
Posted by: step back | August 05, 2011 at 02:57 PM
Dear step:
I agree that lay judges have some of the same problems as the rest of the public in understanding technology. But Federal Circuit judges do better than most; I think Judge Bryson simply got caught up in the while genome sequencing argument and was trying to make a "pro-technoloy/pro-innovation" decision.
Thanks for the comment.
Posted by: Kevin E. Noonan | August 05, 2011 at 09:02 PM
Kevin, regarding your comment about the 15mer claim, are you construing the claim to require that the 15 nucleotides be consecutive? That's the only way the claim has any possible validity. Assuming you are reading "consecutive" into the claim, are you saying that there is at least one published sequence out there (published prior to the filing date) that discloses 15 consecutive nucleotides of the cDNA? Have you actually checked into this? 15 is pretty short, but 1994/95 was a long time ago...
Or are you reading "consecutive saying the claim is invalid because the word "consecutive" is omitted, or are you reading "consecutive" into the claim and instead saying that it fails 102 (due to previously disclosed sequences)? The "consecutive" issue is sort of a big issue. If the 15 nucleotides are not consecutive, then what the heck
Posted by: Gary Johnston | August 07, 2011 at 05:23 PM
Ignore last paragraph -- something weird happened with the post.
Posted by: Gary Johnston | August 07, 2011 at 08:31 PM
Dear Gary:
First, the information comes from Bob Cook-Deegan - I wrote about it on March 30, 2010 (see www.patentdocs.org/2010/03/caught-in-a-time-warp-the-invalidity-of-brca1-oligonucleotide-claims.html?cid=6a00d83451ca1469e20133ec6192bb970b). From what I recall, he found several 15-mers that were part of other genes known at that time.
I think (and am writing a post) that one of the problems in this case was the failure to construe the claims - much of the debate has to do with one side or the other working from an interpretation of the claim that goes against the "ordinary and customary" meaning of the terms as they are used in the art (both biotechnology and biotechnology patent law). I do "read into" the claims that the nucleotides are consecutive, because any random series of nucleotides of whatever size can be gleaned from any sequence, taking away all specificity for the BRCA gene.
Thanks for the comment.
Posted by: Kevin E. Noonan | August 07, 2011 at 09:29 PM
Kevin: Forgot about that post. Seems no doubt that the claim is invalid. It's not really important one way or the other since neither this claim nor the full-length claim would be infringed by performance of a sequencing based test (at least the way Myriad does it). The real issue concerns the correlation claims. This panel killed them, and although the panel absolutely reached the correct result, it's reasoning was totally incorrect (it's all going to get hashed out anyway in Prometheus). I saw an article where Dr. Cook-Deegan characterized as disingenuous Myriad's public statements that the decision regarding the correlation claims was immaterial. He's right. These claims are really the whole ballgame. The only problem (which is not insignificant) for competitors is the proprietary mutations. In the course of doing its test, Myriad has discovered and characterized many mutations that the public knows nothing about.
Posted by: Gary Johnston | August 07, 2011 at 10:52 PM