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Patenting Biologicals: Myriad Issues and Options in the Wake of Myriad

Science, like law, is in pursuit of an esthetic of symmetry wherein the apparent messiness of natural phenomena and human behavior can be reified into results that closely approximate if not capture the forms of truth and justice. When the two esthetics intersect, as in debates about patent eligibility of biologicals, the challenges are rich for lawyers, scientists, and lay citizens alike.

Press reports of a Supreme Court decision last June dramatically proclaimed “Corporations Don’t Own Your Genes” or “Genes Are Not Patentable.”  While these reports of Association for Molecular Pathology, et al. v. Myriad Genetics, Inc., et al.1 (Myriad) certainly captured public attention, they fell short of telling the full story. Attention-grabbing headlines are short and dramatic, but can mislead, misinform, and sometimes be outright wrong. Unfortunately, many readers never make it past a headline, and often when they do, the headline is the only thing remembered of the news event.

The Myriad decision in fact raises many interesting questions about what may or may not be patent-eligible as the opinion navigates the complexities of the underlying science and law.  Appreciating these nuances and the challenges posed can not only aid the patent attorney, as a practical matter, but also the general practitioner or citizen who understandably want to believe in both law and science as consistent and elegant.

Considered from a historical and legal perspective, the true impact of the Myriad decision comes into focus.  While the underlying science is complex, not unlike patent law itself, neither is so impenetrable as some would allege, and the insights to be gained on policy issues of general concern make the analysis worth the effort.

Historical Background

In short, the Myriad case was about “patent-eligible” subject matter. As explained below, not all things are eligible for a U.S. patent grant. Patent-eligible subject matter is defined by 35 U.S.C. §101.  Section 101 identifies four categories of patent-eligible subject matter: a process, a machine, a manufacture, and a composition of matter.  These four categories date back to the original patent statute drafted by Thomas Jefferson in the Patent Act of 1793 (Jefferson originally used the phrase “useful arts,” which was replaced with “process” by the Patent Act of 1852). All things patentable must fall within at least one of these four categories. Once claims have been determined to be patent-eligible, the patentability inquiry proceeds to examination for novelty and nonobviousness.2

In the 1850s, the United States Supreme Court rendered two decisions that excluded three subject areas from the four categories: laws of nature, physical phenomena, and abstract ideas.3 But the U.S. Patent Office in 1873 accepted that microorganisms may be patented when it issued U.S. Patent 141,072 to Louis Pasteur in 1873. The Pasteur patent was directed to a “yeast, free from organic germs or disease, as an article of manufacture.”4 Assumedly, the yeast being claimed was an organism not found in nature since it was “free from organic germs or disease.”

As one would expect, the attempts to patent such subject matter after Pasteur’s patent issued were few and far between. One notable example that came close is U.S. Patent 634,423.5 The ’423 patent claimed use of anaerobic bacteria in a septic tank. The issue of whether the claims were directed to eligible subject matter was litigated. The 2nd Circuit Court of Appeals rejected the infringer’s claim that this patent claimed a process of nature that had been known for ages. The court stated that the inventor claimed a method of subjecting the anaerobic bacteria to flowing sewage in a manner that maximized the bacteria’s efficiency. Since the claim was for the method, the subject matter was patent-eligible. Not surprisingly, this patent did not contain any claims to the bacterium itself, but instead to a method, apparatus, and combination of the bacteria and the septic tank. Other patents also claim uses of naturally occurring organisms, but do not claim the organism itself. See, for example, U.S. 1,894,135 (patenting a dough composition and a baked bread product); 1,980,083 (a yeast composition and process of making); and 3,013,946 (a process of preparing a composition of spores).

Expanded Definition

In the early 1970s, the Patent & Trademark Office (PTO) changed its internal policy with respect to patenting living organisms. This was about the same time genetically modified organism technology was in its infancy. This policy set the stage for the decision in Diamond v. Chakrabarty, involving patent eligibility of a genetically modified bacterium.6

A scientist, Ananda Mohan Chakrabarty, developed a genetically engineered organism using plasmid transfer technology while working at General Electric. But when they applied for a patent, the patent application was rejected due to the Patent Office policy that a microorganism was not patentable subject matter. The applicants appealed to the Court of Customs and Patent Appeals (CCPA),7 which then had jurisdiction. In overturning the Patent Office’s decision, the CCPA cited Application of Bergy, in which the CCPA stated, “The fact that microorganisms, as distinguished from chemical compounds, are alive is a distinction without legal significance.”8 The commissioner of patents at the time, Sydney Diamond, then appealed to the Supreme Court.

In Chakrabarty, scientists added four DNA plasmids to a bacterium, enabling the bacterium to break down various components of crude oil.9 The Supreme Court, in a 5-4 decision, held that the modified bacterium was patent-eligible. The Court explained that the patent claim was “not to a hitherto unknown natural phenomenon, but to a nonnaturally occurring manufacture or composition of matter—a product of human ingenuity ‘having a distinctive name, character [and] use.’”10 So the Court’s position was that the genetically modified organism fell into two patent-eligible subject matter classes (manufacture and composition of matter). Chakrabarty, as the decision is known, paved the way for patents on genetically modified microorganisms and other life forms. Following the Court’s Chakrabarty guidance, the PTO determined that living materials were eligible for patenting when the living material is a “human-made invention.”  Thus, isolated cell lines, isolated tissues, animals, and plants were eligible for patenting under §101, and such claims would be examined for patentability according to Title 35 (the patent statute) as would any other patent application.

The PTO concluded that human beings were not within the scope of §101, and published a notice in the PTO’s Official Gazette advising the public of its conclusion.11 The notice advised that “A claim directed to or including within its scope a human being will not be considered to be patentable subject matter under 35 U.S.C. §101.”12

Despite the Court holdings and PTO rules, research and development in related fields continues, albeit along slightly deviated paths. One illustrative example is U.S. Patent 4,736,866 (1988), known widely as the “Oncomouse patent.”13 Claim 1 of this patent claimed “a transgenic non-human mammal whose germ cells and somatic cells contain a re-combinant activated oncogene sequence introduced into said mammal.” Basically, a mouse was genetically modified to carry specific genes, resulting in a mouse more suitable for cancer research. The patent claims explicitly excluded humans while including other mammals, which complied with the PTO policy.

Evolving Criteria

In subsequent years, the Supreme Court continued to wrestle with the issues of patent-eligible subject matter but the focus of its efforts shifted from biotechnology to software.14  The outcome of the decisions in Bilski v. Kappos and Diamond v. Diehr was a series of tests for patent-eligible subject matter designed to encompass all four categories in §101.  While these tests and a subsequent biotech decision, Mayo Collaborative Services v. Prometheus Laboratories, Inc.15 (Mayo) are beyond the scope of this article, suffice to say that none of these was less than controversial. The decisions in Bilski and in Mayo were especially criticized.  Bilski, was criticized for positing what many thought to be an unworkable and vague test, whereas Mayo was criticized for its perceived destabilizing effect on the biotech industry.16 Against this background, the Court in Myriad held back and the decision was anything but broad, despite all the headlines.

The Myriad Court relied heavily on Diamond v. Chakrabarty and only mentioned the Mayo case in passing, primarily for background and a historical perspective.17 As such, the Myriad holding suggests that the Court may have been reluctant to issue another all-encompassing decision in the wake of the controversy surrounding Bilski and Diamond v. Diehr, such as further elaborating abstractly on one of their previous tests on patent-eligible subject matter or giving us another broad test to contemplate and criticize; nor apparently did it want to elaborate on Mayo.  The Myriad decision appears to be fairly narrow and fact-specific; however, even a narrow and fact-specific decision by the Supreme Court can leave open a lot of room for debate and maneuvering.

Myriad Decision

So what was the Myriad decision about? Myriad discovered the precise location and sequence of two genes known as BRCA1 and BRCA2.  Mutations in these genes dramatically increase an individual’s risk of breast cancer.  This discovery enabled Myriad to develop tests for detecting mutations in BRCA1 and BRCA2 and therefore providing an indication of increased risk of breast cancer.18

The Supreme Court in Myriad unanimously held that, “A naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated, but cDNA is patent eligible because it is not naturally occurring.”19 Justice Thomas’s opinion was not long (18 pages) and all the justices agreed. There was one concurring opinion (Justice Scalia) and it related to his limited understanding of the technology and not to a differing view. Justice Thomas appears to have gone out of his way to ensure a logical progression of his opinion in view of Chakrabarty.

Isolated DNA. Comparing the cleaved (isolated) DNA strand of Myriad to the subject matter of Chakrabarty, Justice Thomas stated “In this case, by contrast, Myriad did not create anything. To be sure, it found an important and useful gene, but separating that gene from its surrounding genetic material is not an act of invention.”20

So even though the location of the gene claimed in the Myriad patent was not known prior to Myriad’s discovery, the discovery in itself of the gene is not enough for the gene itself to be considered patent-eligible subject matter. Justice Thomas also stated “[N]or are Myriad’s claims saved by the fact that isolating DNA from the human genome severs chemical bonds and thereby creates a nonnaturally occurring molecule.”21 Justice Thomas’ statement above is actually consistent with the holding in Chakrabarty. The Court in Chakrabarty stated that “… the relevant distinction was not between living and inanimate things, but between products of nature, whether living or not, and human-made inventions” and that Chakrabarty’s “micro-organism is the result of human ingenuity and research.”22

In Chakrabarty, the bacterium was referred to as a human-made, genetically engineered bacterium. In Myriad, the genes were cleaved from the genome, and probably just as important, the genes were being claimed by an alphanumeric designation rather than by any chemical structure or functionality. The Myriad claims did not contain any language of human ingenuity or intervention except for the isolation of the gene. “Myriad’s claims are simply not expressed in terms of chemical composition, nor do they rely in any way on the chemical changes that result from the isolation of a particular section of DNA. Instead, the claims understandably focus on the genetic information encoded in the BRCA1 and BRCA2 genes.”23 Would the justices have opined differently if the gene was claimed differently?

What isn’t as clear from the decision in Myriad is why it was apparently significant to Justice Thomas that a potential infringer could not avoid the patent claims. Justice Thomas notes that even if the potential infringer created a new and unique molecule, since both the BRCA1 and BRCA2 genes would be contained in any variation, (such as adding an additional nucleotide pair to these genes), any such variation would infringe the Myriad patents if found valid.24 It is puzzling why the fact that a potential infringer would have no way to get around a patent claim would be important to Justice Thomas or relevant to the Court’s interpretation of 35 U.S.C. §101 definitions of patent-eligible subject matter. Why should that matter? Isn’t the quality of a patent claim judged by how difficult it is to avoid infringement?

Not Naturally Occurring cDNA. The Court affirmed the CAFC’s holding that cDNA is patent-eligible subject matter. This was based on the fact
“[A]s already explained, creation of a cDNA sequence from mRNA results in an exons-only molecule that is not naturally occurring.”25 In coming to this conclusion, Justice Thomas rebuffed the petitioners’ arguments that “cDNA is not patent eligible because ‘[t]he nucleotide sequence of cDNA is dictated by nature, not by the lab technician.’”26 Justice Thomas acknowledged the basic proposition of this argument may be true, however “cDNA retains the naturally occurring exons of DNA, but it is distinct from the DNA from which it was derived. As a result, cDNA is not a “product of nature” and is patent eligible under §101.”27 Justice Thomas indicates that the line with respect to human ingenuity and intervention exists between isolating DNA and removing the introns to create an exons-only molecule.

Justice Thomas qualified this statement by further stating, “… except insofar as very short series of DNA may have no intervening introns to remove when creating cDNA. In that situation, a short strand of cDNA may be indistinguishable from natural DNA.”28 So in certain situations, such as when no exon(s) are removed, cDNA may not be considered patent-eligible subject matter.

Distinguishing the DNA and the cDNA of the Myriad patent claims, the Court’s decision seems to accept the reasoning of Chakrabarty that “a man-made product, relying partially on nature, [as distinct] from one merely taken wholly from nature, is patentable subject matter.”29

Related Issues. Justice Thomas made three points in dicta in the latter part of his opinion.  First, he noted that there were no method claims before the court. As he stated “[H]ad Myriad created an innovative method of manipulating genes while searching for the BRCA1 and BRCA2 genes, it could possibly have sought a method patent.”30

The mere mention of a gene by its known name in a patent claim will not render the claim per se patent-ineligible subject matter. Further, an innovative method of isolating a particular gene appears to be patent-eligible subject matter under Justice Thomas’ opinion and is consistent with the earlier Mayo holding. The second point by Justice Thomas was that the case before the Supreme Court did not involve the patents directed to new applications of knowledge relating to BRCA1 and BRCA2 genes. He acknowledged that Myriad had unchallenged patent claims in this area.

The third and last point he made was that the court did not “… consider the patentability of DNA in which the order of the naturally occurring nucleotides has been altered. Scientific alteration of the genetic code presents a different inquiry, and we express no opinion about the application of §101 to such endeavors.”31

The Take Away

The effect of the Supreme Court’s opinion in AMP v. Myriad is to make claiming naturally occurring cleaved (isolated) DNA patent-ineligible.  So what is patent-eligible?

cDNA is positively patent-eligible when introns have been removed from the naturally occurring DNA to make the cDNA. The opinion says so. We are left to debate the area in between. Based on the explanation of Chakrabarty in this decision, there appears to be considerable latitude in trying to protect intellectual property related to a particular gene.

If the order of the naturally occurring nucleotides were altered, then such a molecule would be considered “human-made” and thus patent-eligible subject matter under 35 U.S.C. §101. (Even though Justice Thomas made no definitive conclusion). Also under the logic of this decision, if the order of the nucleotides were changed, such changes presumably would have to be recited in the claims in a manner considered as identifying the chemical structure of the altered nucleotide sequence and that would appear to be patent-eligible.

Even what may be a narrow decision by the Court can have far-reaching consequences.  While Myriad discussed what was patent-eligible or ineligible subject matter, the decision blurred the distinction as applied to the patent eligibility of a number of other types of matter, for example, bacterial genes.
Bacterial genes do not contain introns and therefore, do not have cDNA constructs similar to human genes.  The cDNA sequence synthesized from bacterial mRNA results in a cDNA sequence that is identical to naturally occurring bacterial DNA.  Similar human ingenuity and intervention are needed in working with both bacterial and human genes, but with human genes, a cDNA sequence that is different from naturally occurring DNA is obtained. Is cDNA obtained from human genes and mRNA patent-eligible while DNA obtained from bacterial mRNA is patent-ineligible? This does not seem consistent.  In addition, are drugs or proteins isolated from naturally occurring microorganisms or plants patentable?  If not, the biotechnology world would truly be turned upside down. These inconsistencies or nuances are what make even a narrow and fact-specific decision such as Myriad far-reaching.

After Myriad, patent claims directed to unique methods for isolating a gene and/or use of a gene should be patent-eligible.  Patent claims defining a kit that contains the DNA and other components might be patent-eligible.  Analogous to claiming molecules purified from naturally occurring microorganisms, perhaps composition claims to DNA defined by the chemical structure and at high concentrations not found in nature are patentable.  A diagnostic test that utilizes all or part of the DNA could also be patent-eligible. These are exemplary suggestions and there undoubtedly are many other ways, given a particular set of facts, by which a perceptive patent attorney can obtain patent protection for a client.

While many questions remain outstanding, there are still many choices available to protect DNA-related research. What should now be clear without question is that headlines such as “Corporations Don’t Own Your Genes” and “Genes are Not Patentable” fail to capture the issues at hand. Neither headline is based on careful thought.  As Lennon and McCartney observed, “Living is easy with eyes closed, Misunderstanding all you see … .”

Z. Peter Sawicki is an intellectual property attorney, and shareholder at the Minneapolis law firm of Westman, Champlin & Koehler, PA. 

 

Visala C. Goswitz is a patent agent with the law firm of Westman, Champlin & Koehler, PA. She also has a Ph.D in Biochemistry.

 

Amanda Prose is an intellectual property attorney at the Minneapolis law firm of Westman, Champlin & Koehler, PA. 

Notes

 

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