[Ip-health] Patently-O Guest Post from Senior Director of Legal Affairs of Myriad Genetics, Inc.

Reshma Ramachandran reshmagar at gmail.com
Wed May 1 06:43:28 PDT 2013


Guest Post: Nine Reasons why the Supreme Court Should Side with Myriad and Affirm the Patenting of Isolated Human Genes
Posted: 30 Apr 2013 09:00 PM PDT
Guest Post by Benjamin Jackson, Senior Director of Legal Affairs at Myriad Genetics, Inc.

The Myriad Case: A Golden Opportunity to Bring Clarity and Fairness to Subject-Matter Eligibility

Two weeks ago the US Supreme Court heard oral argument in the landmark case ofAMP v. Myriad Genetics. The Justices appeared engaged in the argument and seemed to be genuinely seeking understanding of the science and the potential impact of any decision they might take. Several specific points emerged from the argument that warrant further discussion:

1. What Does "Isolation" Really Mean? Some Justices seemed to struggle with what is involved in "isolation" under the patents. This is the most critical issue in the case as a correct understanding of this word leads to the inescapable conclusion that the claims are directed to human-made inventions rather than what exists in nature. Regardless of any meaning used in the Petitioner's arguments and those of prominent amici such as Dr. Lander, "isolation" as defined by the patents requires that a new chemical entity be created either synthetically from scratch or by chemically/structurally modifying an existing molecule. The patents explicitly define "isolated" DNA as removed from its natural environment, whether that environment be in the nucleus or, as the Lander brief emphasizes, floating around outside the cell in someone's blood. But isolation under the patents is not just "snipping" molecules as they sit in their natural environment. Isolation under the patents also requires purification (i.e., concentration) of the newly created molecule out of the interfering milieu.

What is ignored in ACLU's arguments is that purification is a critical element of what it means to "isolate" something under the patents. The Lander brief calls purification of DNA routine, but only in the context of randomly purifying allnucleic acids out of a sample. "Isolation" under the patents requires specific, targeted purification/enrichment of BRCA1- or BRCA2-related molecules, which was not routine or even possible before Myriad's invention. Under this proper understanding of everything that "isolation" under the patent requires, ACLU made Myriad's case by conceding in their reply brief and in oral argument that purification to yield a significant new utility is sufficient to warrant a patent. Some Justices seemed to agree: A molecule sitting in a leaf of an Amazonian plant is not "new" or patent-eligible, but it becomes both once it is purified and concentrated into a useful form. Similarly, DNA in its natural environment, whether whole in the cell or fragmented in the blood, is neither new nor patent-eligible, while a DNA molecule chemically modified and purified by man is both.

2. Splitting the Baby Doesn't Work Out Well for the Baby. Some see patent-eligibility for cDNA and not isolated genomic DNA, advocated by the Department of Justice, as a compromise position that the Court is seriously considering. I am hopeful that instead the Court has merely recognized that cDNA is so clearly patent-eligible that it needs no serious discussion and has efficiently moved on to the marginally closer question of isolated genomic DNA. While this may superficially seem like a nice, neat compromise, it quickly falls apart under scrutiny. In the area where the Myriad case has the most potential impact, because new isolated DNA patents are common and thus incentivizing new discoveries is most important today, there is no distinction between genomic DNA and cDNA. Bacteria, for example, have no introns, which means the reverse transcription product of mRNA (i.e., what you might call a cDNA) has a sequence identical to genomic DNA. In essence, there is no such thing as cDNA in bacteria. DOJ's position would make all isolated DNA claims patent-ineligible in any organism without introns. The wisdom of Solomon was not in splitting the baby, but in finding a course that meant he didn't need to.

3. Methods v. Compositions. Much of the Myriad oral argument centered on whether method of use claims would be enough to incentivize innovation in the life sciences. Some Justices seemed to be trying to weigh whether an entire category of composition claims could be invalidated without negative effect on innovation because method of use claims would remain. With respect, the Court is not the body that can or should attempt these kinds of determinations where in-depth investigation and careful balancing of competing interests is needed to strike the right balance between what is or is not needed for innovation. For example, the Court is not well-positioned to survey in detail the international legal landscape to,e.g., evaluate statements such as those from DOJ on DNA use versus composition patents in Europe. Congress, not the Court, is practically equipped and Constitutionally-tasked with precisely this type of determination.

4. Analogies. The Court seemed to grapple with several analogies in trying to probe the outer reaches of patent-eligibility. Any analogy that overly simplifies complex science falls apart under close scrutiny. But more importantly, the Court need not agonize over patenting livers cut out of bodies or whole plants uprooted from the Amazon. The patented molecules in Myriad are far closer and vastly more analogous to the chemical compound purified and concentrated from the Amazonian plant than the uprooted whole plant. Indeed, Myriad's claims present an even stronger case because there has been a modification of the chemical structure in addition to the purification. We must not confuse the analogy for the thing actually at issue or let hypothetical future implications of questionable likelihood cloud what was actually patented in this case. Concerns over allowing patenting of extracted livers should not distract the Court from the simple fact that what is before it in Myriad is neither an extracted liver nor an uprooted plant, but instead a highly useful, purified and chemically modified compound that never existed in nature until Myriad created it. If someone ever tries to patent an extracted liver, the Court can address any problems then. It would be tragic, however, to let the "tail" of that remote future possibility wag the "dog" of patent-eligibility for biotech inventions today.

5. Innovation. Some Justices appeared anxious incentivizing innovation without inhibiting it, with Justice Breyer noting "uncomfortable compromises" in patent law. The Myriad patents specifically and gene patents generally require no such discomfort. First, ACLU's argument that the claims preclude any study of the BRCA genes is simply wrong. Untargeted sequencing and analysis of the genes would not infringe claims to isolated BRCA DNA because it does not involve purification (thus no "isolation") of the BRCA genes out of the genomic milieu. Second, putting ACLU's anecdotes aside, all available systematic evidence shows that gene patents do not inhibit but instead spur innovation. ACLU's imaginative assertions about what the claimed molecules can be used for are a red herring; the Petitioners inMyriad clearly stated in their declarations that they want to use the claimed molecules not for DNA-based computers or developing new drugs, but instead to replicate Myriad's test.

6. Every Chemical Invention Is Possible in Nature. Justice Alito made an insightful comment about a branch washing up on shore looking like a baseball bat. This shows the legal irrelevance of the Lander amicus brief, which figured somewhat prominently in the oral argument. That randomly fragmented DNA floating around in someone's blood might at some point comprise the BRCA1 gene is irrelevant to the question whether what Myriad claimed was produced by human ingenuity rather than by nature. The relevant question is whether the inventor merely found something unmodified in nature and staked claim to it, or insteadcreated something by her own ingenuity. To ask whether a claimed chemical composition could conceivably ever exist in nature is an unhelpful question of probability because, given enough time, any arrangement of atoms is inevitable.See, Dan L. Burk, Anticipating Patentable Subject Matter, 65 STAN. L. REV. ONLINE 109, 114 (2013). For example, it was irrelevant to the decision inChakrabarty that Dr. Chakrabarty assisted the natural process bacterial "breeding" that, given enough time, could certainly have yielded the claimed bacterium naturally.

7. Subtraction v. Addition. Many easily accept that combining two chemical entities creates a man-made, patentable invention, but become instantly skeptical if a single molecule is separated into two parts that do not exist in nature. This surfaced in the Myriad argument as well, but from a chemical, biological, genetic, and even legal perspective there is no defensible distinction between addition and subtraction. A molecule created by removing parts that interfered with its new utility is just as much a product of human ingenuity, and can have just as important a new utility, as a molecule created by addition.

8. Short DNA Molecules. Justice Sotomayor asked about claims directed to short DNA molecules of 15 or more nucleotides. She appeared to rely on ACLU's arguments, based on an article published after Myriad filed its merits brief, about these claims covering the entire genome. Certainly as to Claim 6 of the '282 patent, this is clearly wrong. Claim 2 is directed to a molecule with the cDNA sequence of SEQ ID NO:1 (whose patent-eligibility the Court seemed pretty comfortable with) and Claim 6 is merely directed to fragments of that molecule. If the larger molecule is a product of human ingenuity, then human-made fragments of it must also be. Regardless, ACLU's unproven allegations on this point are irrelevant from a practical perspective. Anything as small as 15 nucleotides would only be used as part of a primer pair and, when used this way, the molecules would be 100% specific for BRCA1.

9. Myriad: A Unique Chance to Return Clarity and Fairness to Patent-Eligibility by Returning to the Statute and Chakrabarty. There is currently great confusion amongst courts, the patent office, patentees and the public about patent-eligibility under section 101 of the Patent Act. While the spirit behind the judicial exclusions for patentability is correct, decisions applying them can often be, in the words of Justice Frankfurter, "infected with too much ambiguity and equivocation" due to "vague and malleable terms" such as "the work of nature" and the "laws of nature." But the language of section 101 itself and the Court's seminal decision in Diamond v. Chakrabarty provide the Court with a framework for a long overdue recalibration and clarification of patent-eligibility in the Myriad case.

Section 101 requires that a claimed composition of matter be both new and useful, thus encompassing the judicial exclusions and giving courts the tools to resolve difficult questions of patent-eligibility. The claimed chemical composition must have some structural, physical or chemical change from the natural starting materials used by the inventor in order to be new under section 101. Limiting patent-eligibility to structurally, physically, or chemically "new" things addresses the judicial concern over patentees removing from the public domain that which exists in nature because there must be a modification of the natural thing. It further addresses the Mayo Court's concern over section 101 becoming a dead letter. Section 101 fills the gap in sections 102 and 103 by excluding anything the inventor found in nature but that was not previously known to others (which could not be anticipated or obvious under section 102 or 103, but which we don't want to award a patent for).

Merely being new is not enough under section 101; the claimed invention must also be useful. This is where the statute really does its work and gives courts an objective yet flexible framework for giving proper force to the legislature's intent. Not just any utility will do. The claimed composition must have one or moresignificant new utilities and these new utilities must directly result from the structural, physical or chemical changes made by the inventor. Courts can exert substantial discretion in determining whether the new utilities are "significant" under section 101. Courts can weigh the structural changes (how new the composition is) with the new utilities (how significant they are) to decide whether the invention is patent-eligible. If the utility is relatively minor, more of a structural change may be required. If the utility is groundbreaking, very minor structural changes may be sufficient. For example, purification of a molecule from its natural surroundings, without any change in the chemical structure, is a relatively minor structural/physical change from the natural state of things. Nevertheless, this may be patentable if the highly purified composition has significant new (e.g., therapeutic, diagnostic) uses. Importantly, these uses must be assessed from the perspective of human endeavors. The purified molecule always has some or all of the same chemical properties (e.g., polarity, electronegativity, etc.) as it did in nature, but its purification has opened up a world of human uses that take advantage of those properties.

The Court's decision in Chakrabarty, the definitive statement of patentable subject matter for compositions of matter, epitomizes the judicial exclusions and the statute working at their harmonious best. Chakrabarty cited to many of the early cases that established the judicial exclusions from patent-eligibility, then clarified that the dispositive question for patent-eligibility is whether what is claimed is a product of nature or a product of human ingenuity. The Court's analysis paralleled section 101's text, emphasizing that the claimed bacterium was different from what existed in nature (i.e., it was new) and had "significant utility" (i.e., it was useful).

In a great insight into what it means for something to be "new" under section 101, the Court made clear that it is the differences between what is claimed and what exists in nature, not the similarities, that make all the difference in patent-eligibility. Dr. Chakrabarty manipulated bacterial breeding to give one bacterium the natural ability of other bacteria to eat oil. As Dr. Chakrabarty himself noted in his amicus brief in support of Myriad, "the genetically-engineered bacterium that I created and sought to patent in Chakrabarty had a quite similar structure to what existed in nature. It shared the same genome and internal structure as naturally occurring Pseudomonas bacteria and differed only by a few pieces of DNA."

But these elegant changes resulted in "significant utility" such that the Court declared that these modest modifications yielded a product that was "markedly different." The vast similarities were irrelevant; they did not negate the fact Dr. Chakrabarty's human ingenuity brought about something that never existed before with "a distinctive name, character and use." As the Chakrabarty Court noted, legislative history makes clear that what is not eligible for patenting is that which is "created wholly by nature unassisted by man" while anything that "is unique,isolated, and is not repeated by nature, nor can it be reproduced by nature unaided by man" is eligible. The modified bacterium gained significant utility from the donor bacteria and could now be put to many important new uses (e.g., cleaning up oil spills). Again, a relatively minor structural change can be enough if the gained utility is significant.

In Myriad, the Court can readily apply this framework to find that the claimed compositions are new and useful and thus patent-eligible. The isolated DNA molecules are new because they are not found in nature by definition. As shown in point # 1 above, "isolation" under the patents requires a brand new chemical composition with significant structural changes that has been purified and concentrated out of the milieu that previously prevented its new uses. Chromosomal DNA in its natural environment, whether whole in the cell or fragmented in the blood, is neither new nor patent-eligible, while the molecule chemically modified and purified by man is both.

The new molecules have gained significant new utilities. They can be used as laboratory tools for targeted sequencing of the BRCA genes of patients, which is not just transfer of an existing utility to a new product as in Chakrabarty, but anentirely new utility never possible before. ACLU makes much of the fact that these utilities largely depend on properties shared with the natural DNA. This is true but irrelevant. The new molecules share some useful properties with the natural source material (why else would we have sought them out?), but the breakthrough new utilities were impossible before the inventors' modifications. This is precisely what the patent system was designed to incentivize.

Upholding the Myriad patents does a lot more than affirm patent protection of a deserving invention of human-made molecules with significant societal value. InMyriad the Court can honor the language and intent of the statute passed by Congress and bring the objectivity, clarity and predictability that patentees and alleged infringers alike yearn for, all while advancing the policy goals of the judicially-created patent-eligibility exclusions.

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