By David Mellman, Ph.D and Mary Breen Smith
Note: please see update (published June 4, 2014) with regards to this issue.
In June 2013, the U.S. Supreme Court held in Association for Molecular Pathology vs. Myriad Genetics, Inc., No. 12-398 (569 U.S. ___ June 13, 2013) that isolated genomic DNA sequences that are identical to those found in nature are not patent eligible subject matter under 35 U.S.C. § 101. This decision overturned years of established practice by the U.S. Patent and Trademark Office, which had previously determined that isolation of genomic DNA from its natural state rendered the DNA sequence patent eligible subject matter. The scope of the Myriad decision will not only affect patents in the field of human medicine, but will also likely affect patents in the fields of veterinary medicine, agriculture, food and beverage manufacturing, biochemical and enzyme manufacturing, and bioenergy.
After Myriad, it is clear that claims to isolated genomic DNA segments that are identical to those found in nature are no longer patent eligible subject matter. The Court held that complementary DNA, or “cDNA,” a synthetic form of DNA, however, still meets the threshold test for patent eligible subject matter. This is because the composition of, and the genetic information stored in the cDNA is not found in nature, rather it results from human innovation. Therefore, cDNA does not present the same obstacles to patentability as naturally occurring, isolated DNA segments.
While this ruling is a major change in the law, industry and academia’s emphasis on patents to isolated genomic DNA has been declining in recent years. The number of patents granted to isolated genomic DNA having sequences identical to those found in nature, peaked in 1999. Since 2005, the number of issued patents claiming sequences of isolated genomic DNA has been an average of about 600 per year. In recent years, industry and academia have instead focused their interest on therapeutic molecules such as proteins, peptides, RNAs, and transformed organisms containing exogenous cDNA, and their associated methods of use. In many cases, these biological materials are also similar or identical to those found in nature.
In light of Myriad, one of the primary questions left unanswered about these other classes of naturally occurring biological molecules is whether they remain patent eligible subject matter. Our view is that these other natural molecules remain patentable despite “the product of nature” doctrine as interpreted by the Myriad Court. This is because the Court expressly limited its holding to “genes and the information they encode” when only “isolated from the surrounding genetic material.” Therefore, molecules that have been modified from that occurring in nature, and/or have a functional component that is applicable from human knowledge and innovation, rather than merely acting as a storage component of genetic information found in nature, should remain patentable.
However, practitioners will not know the scope of Myriad for certain until cases concerning these other naturally occurring molecules have made their way through the courts. In the meantime, we recommend some strategies to distinguish claimed natural molecules from being viewed similarly as the genomic DNA of Myriad. For DNA molecules, we recommend describing the distinctive chemical structure or properties of the claimed molecule and how it differs from molecules in nature. For example, when claiming DNA sequences, it is advisable to claim the cDNA sequence, which lacks the non-coding intronic region. Labeled nucleic acids used for detection methodology such as labeled products, tags and probes will likely be patent eligible, as these are non-naturally occurring sequences. Similarly, artificial DNA such as hybrid or fusion molecules, or recombinant DNA in the form of vectors, should remain patentable.
With regard to patenting RNA molecules, we note that RNA molecules which are identical to those found in nature should remain patentable since these molecules have both an information component and an applied functional component. This would include antisense RNAs, siRNAs, micro-RNAs and the like. Suggestions to further distance one’s claims from the limitations of the Myriad decision, is to draft claims to “synthetic” rather than “isolated” molecules, and using “consisting of” rather than “comprising” to distinguish claimed short stretches of RNA from reading on larger molecules containing those stretches. We note that in many cases a therapeutic interest centers on chemically modified RNAs, and as these differ from RNAs found in nature, there should not be a Myriad issue with these sequences.
With regard to isolated proteins and peptides, where the amino acid sequence being claimed is identical to a native protein, an option would be to recite the terms “recombinant” or “synthetic” sequences in the claims, rather than reciting the “isolated” sequences. Recombinant proteins generally are glycosylated and these modified glycosylation patterns will vary from the native protein, leading to a non-naturally occurring molecule. Mutagenized or derivitized peptides or proteins that differ from the natural parent molecule should also remain patentable. The more human modification applied to a molecule of interest, the less likelihood of facing limitations imposed by the Myriad decision.
Another question that remains after the Myriad decision is its effect on the patentability of natural compounds having therapeutic activity extracted from exotic plants. Patent litigation defendants will likely try to use the Myriad ruling to challenge the validity of claims covering these naturally occurring compounds from plants. However, the Supreme Court’s decision was specifically limited to isolated genomic DNA. As the Court stated, isolated genomic DNA and the genetic information encoded within the genes are not patent eligible. In contrast, molecules such as purified compounds from plants do not act to store genetic information. Rather through human innovation they have a functional component relevant to their applied use, thus these purified compounds from plants will likely remain patent eligible.
A known consequence of the Myriad decision will be that granted U.S. patents claiming isolated genomic DNA molecules will face potential invalidation. In light of this consequence, there may be an increase in the filing of reissue applications by patent holders in order to narrow the scope of the claims to cover cDNAs of interest. Another consequence of this decision may be an increase in inter partes review requests by competitors and licensees in order to invalidate the claims relating to isolated nucleic acid molecules. Until the USPTO and U.S. courts clarify the boundaries of patent eligible subject matter, patent applicants pursuing claims that include a “product of nature” would be wise to present a wide variety of claims with varying scope and varying focus.
Looking ahead, patent applicants seeking to claim a naturally occurring substance should avoid language that simply details the iterative process of discovering that substance. Additionally, claims that merely relate to naturally occurring sequences in their U.S. patent application should be avoided. Instead, the patent claims should be directed to cDNAs, as well as claims on new functional applications of naturally occurring nucleic acids, proteins, and small molecules of interest. As for isolated genomic DNA specifically, a consideration resulting from the Myriad decision may be a greater reliance on trade secrets rather than patents, although another consideration is that isolated genomic DNA molecules are still patent eligible in Europe and in many other countries around the world.