For over 30 years, it was believed that an isolated and purified DNA sequence possessing the same sequence as a naturally occurring gene was eligible for patent protection. On June 13, the U.S. Supreme Court held patent claims covering isolated naturally occurring DNA were not patent eligible. Since the court’s decision, debate continues about what constitutes patentable subject matter.

Prelude

In 1998, Myriad Genetics was granted a patent that covered mutations to the BRCA1 and BRCA2 genes (breast cancer genes). The patent also covered methods for: (i) using these mutations for diagnosis and prognosis for breast and ovarian cancer; (ii) screening for cancer predisposition; and (iii) developing therapeutic cancer treatments.

In 2009, the American Civil Liberties Union, on behalf of the Association for Molecular Pathology and others, filed a lawsuit against Myriad, the U.S. Patent and Trademark Office (USPTO), and the University of Utah, seeking declaration that Myriad’s breast cancer gene patents were invalid. Specifically, the plaintiffs argued that the isolated DNA and sequence for thebreast cancer genes are products of nature and, thus, unpatentable subject matter. A nonpatentable product of nature includes mathematical formulas, laws of nature or natural phenomena, such as a mineral or plant organism, even if newly discovered. 35 U.S.C. §101.

Myriad motioned the court to dismiss the complaint, arguing that the plaintiffs lacked standing. In order to establish standing to bring a declaratory judgment action, a plaintiff must demonstrate that an immediate and substantial controversy exists between the parties. MedImmune v. Genetech, 549 U.S. 118 (2007). Declaratory judgment jurisdiction arises when some affirmative act by a patent owner puts a person in the position of either having to risk pursuing an illegal behavior or abandoning that which he claims he has a right to do. Myriad’s view was there was no real or immediate dispute between the parties because they had only interacted with three of the plaintiffs previously, and those interactions had occurred more than a decade prior to the commencement of the lawsuit. The District Court for the Southern District of New York disagreed, finding that the plaintiffs had standing because under all the circumstances of the case, the plaintiffs’ concern with a possible lawsuit was justified, and because the plaintiffs should not be required to deliberately violate the BRCAbreast cancer gene patent in order to challenge its validity. Ass’n for Molecular Pathology v. USPTO, 669 F.Supp. 2d 365 (S.D.N.Y. 2009).

Act I : Genes Are Not Patentable

Applying a novel interpretation of Diamond v.Chakrabarty, 447 U.S. 303 (1980), the Myriad district court granted declaratory judgment for the plaintiffs. In Chakrabarty, the court stated that because a genetically engineered bacterium is not found anywhere in nature, its creation constitutes a patentable subject matter under §101. The Myriad district court held that because the isolated breast cancer DNA and naturally occurring DNA possess the same “fundamental quality” or biological information, they are not markedly different. Therefore, the court found the breast cancer genes unpatentable subject matter. Ass’n for Molecular Pathology v. USPTO, 702 F.Supp. 2d 181 (S.D.N.Y. 2010).

Based on the “machine or transformation” test, the districtcourt also invalidated the Myriad method claims for comparing or analyzing gene sequences to identify the presence of mutations corresponding to a predisposition to breast or ovarian cancer. The machine or transformation test requires that a claimed process be tied to a particular machine or apparatus, or it transforms a particular article into a different state or thing. In re Bilski, 545 F.3d 943 (Fed. Cir. 2008). The district court held that the Myriad method claims merely constituted a data gathering step. Myriad appealed the district court’s invalidation of its patents to the Federal Circuit and questioned whether the plaintiffs had standing to bring the case in the first place.

Act II: Genes Are Patentable

Regarding the procedural issue of standing, the Federal Circuit found one scientist-plaintiff had sufficient standing to challenge the Myriad patents. The court reversed the district court’s invalidation of Myriad’s breast cancer gene patent claims and methods for screening for potential cancer therapeutics. The court reasoned that because isolated genes, cDNA and partial isolated gene sequences are patentable subject matter under §101 of the Patent Act, Myriad’s claims to BRCA genes and fragments are valid. The court focused on the cleaving of the isolated BRCA DNA out of its chromosomal environment as conclusive evidence of its fundamentally different nature.

The court also held that because the method claims for screening for therapeutics by analyzing growth rates of cells with altered BRCA genes in the presence or absence of the treatments are directed to patentable subject matter, they are also valid. The court, however, affirmed the district court’s decision that Myriad’s methods of “analyzing” BRCAgene sequences and “comparing” with cancer predisposing mutations to normal gene sequences were patent-ineligible because they only cover abstract mental steps. Ass’n for Molecular Pathology v. USPTO, 653 F.3d 1329 (Fed. Cir. 2011). The plaintiffs petitioned the Supreme Court. The court granted certiorari, but immediately vacated and remanded to the Federal Circuit to reconsider in light of its decision in Mayo v. Prometheus, 566 U.S. ___ (2012). In Mayo, the disputed method claims involved administering a drug to treat gastrointestinal autoimmune diseases, determining the concentration of metabolites in the blood, and determining whether to increase or decrease the drug dosage based on the metabolite concentration. The Supreme Court held that patent claims comparing the relationship between naturally produced metabolites and optimal dosages of a therapeutic drug are unpatentable as claiming underlying laws of nature.

On remand from the Supreme Court, the Federal Circuit affirmed its prior Myriad decision.The court again reiterated that the process of removing the BRCA DNA from the human body transformed the DNA molecules into something new and different.The court noted that the Mayo decision was limited to method claims, and thus, not applicable to composition claims like DNA molecules claimed by Myriad. Ass’n for Molecular Pathology v. USPTO, 689 F.3d 1303 (Fed. Cir. 2012). The plaintiffs again petitioned the Supreme Court.

Act III: Human Genes Are Not Patentable

The Supreme Court granted certiorari, but limited the grant to the question of whether human genes are patent eligible. Explaining that Myriad neither created nor altered any of the genetic information of the BRCA genes, the court noted that Myriad found an important and useful gene. The court held that genes and the information they encode are not patent eligible under §101 simply because they have been isolated from the surrounding genetic material.Ass’n for Molecular Pathology v. Myriad Genetics, 653 U.S. 1329 (2013).

Recognizing that human genomic DNA contains protein coding sequences interspersed with noncoding sequences called introns, the court noted that the isolated BRCAgenes contained the same nucleotide sequences, including introns, as found in nature. Therefore, the court found that Myriad’s DNA claim falls within the law of nature exception. Distinguishing other nucleotides, the court determined that cDNA is patent eligible because it is not naturally occurring. cDNA is a synthetic man-made molecule that has the same genetic information as naturally occurring genes, but lacks the introns found in natural genes. Thus, the court concluded that in removing the introns, the laboratory technician creates something new when cDNA is made.

The court emphasized that its decision excluded patent claims involving methods of manipulating genes while searching for the BRCA genes, new applications of knowledge about the BRCA genes, or the patentability of DNA in which the order of the naturally occurring nucleotides has altered.

Epilogue

Although the Myriad court provided limited guidance regarding what constitutes unpatentable DNA subject matter, the court held that naturally occurring human genes are not patent eligible. Notably, the court found that manmade altered sequences like cDNA are patent eligible because cDNA is not naturally occurring. Consequently, practitioners may be tempted to focus on the distinction between natural and nonnatural occurring molecules. The court suggested that patent claims focus on some physical or chemical property of the isolated sequences that is not naturally occurring.

Despite the court’s invalidation of Myriad’s patent claims for breast cancer genes BRCA1 and BRCA2, Myriad continues to enforce its patent. Shortly after the Myriad decision, Ambry Genetics and Gene-by-Gene launched their BRCA mutation tests for breast and ovarian cancer. Myriad filed suits against Ambry Genetics and Gene-by-Gene, alleging infringement of 10 different patents, including the patents challenged in the original lawsuit. In the complaints, Myriad asserted that its remaining patent claims covering BRCAgene testing, including those at issue, pertain to synthetic DNA or methods-of-use, which were not affected by the court’s decision and remain valid and enforceable. The breast cancer gene debate continues. •