September 1, 2013 (Vol. 33, No. 15)
Bernhard D. Saxe, Ph.D., J.D. Foley & Lardner LLP
For superstitious people, the date June 13, 2013, would portend unfavorable events. For chemists and biotechnologists, the date brought a Supreme Court decision that ruled isolated genes to be ineligible for patent protection in the United States, an event with grave consequences for patent law and the biotechnology industry.
The decision, in a unanimous opinion authored by Justice Thomas, reverses years of precedent and U.S. Patent & Trademark Office practice and gives no weight to the chemical structure difference between native chromosomal DNA that contains many genes and an isolated, chemically separate fragment that codes for a single polypeptide.
The case before the Supreme Court is Association for Molecular Pathology et al v Myriad Genetics et al., 569 U.S. ____ (2013). Myriad was granted patents claiming, inter alia, “an isolated DNA coding for a BRCA1 polypeptide,” which has “the amino acid sequence set forth in SEQ ID NO:2” (SEQ ID NO:2 sets forth an amino acid chain 1,863 amino acids long). Another patent claims a similar isolated DNA coding for the BRCA2 polypeptide whose amino acid sequence is recited in the patent.
It is useful to recount the decision of the Court of Appeals for the Federal Circuit case on which certiorari was granted, 689 F. 3d, 1303 (Fed. Cir. 2012). The majority opinion was authored by Judge Alan Lourie, the only chemist of the many judges and justices who ruled on this case, from the beginning to the end.
In the detailed, cogently reasoned 17-page portion of his opinion dealing with the patent eligibility of isolated DNA, he explained that the DNA molecules in chromosome 17 and 113 are about 80 million and 114 million base pairs in length, respectively; they are bound to other molecules in chromatin and packaged in the chromosome; the claimed isolated DNAs are about 80,000 base pairs in length and each codes for a single polypeptide.
The isolated DNAs are not merely purified components of a mixture existing in nature but have to be chemically cleaved from a large molecule and isolated as separate, structurally distinct chemical entities. They are molecules that are produced by making and breaking chemical bonds in the parent chromosomal DNA, and in subsequent smaller chromosomal segments, to produce new molecules that have a different chemical structure from the chromosomal DNA as it exists in nature.
Thus, the claimed isolated DNAs are nonnatural molecules and are therefore eligible for patent protection under 35 U.S.C. 101 (the section of the U.S. patent statute that sets forth what subject matter is patentable) if they satisfy the other statutory criteria for patentability. They are not products of nature, one of the types of subject matter that are not eligible for patent protection.
Judge Lourie viewed the informational content of the new molecules as irrelevant to the threshold issue of patent eligibility but, rather, relevant to the utility of the molecules that may be considered in claims to methods of use and not claims to the molecules themselves.
Judge Moore concurred in the result, but did not agree with Judge Lourie’s chemical rationale. Instead, her concurrence was based on policy grounds, giving deference to Patent Office policy and the effect on the biotechnology industry of a holding of patent ineligibility for isolated genes.
Judge Bryson wrote a dissent that was mirrored in the eventual Supreme Court opinion. In his view, “[T]here is no magic to a chemical bond that requires us to recognize a new product when a chemical bond is created or broken.” He characterized the structural differences as “merely ancillary to the breaking of chemical bonds, a process that is itself not inventive.”
He focused on the fact that the isolated genes have the same genetic code for the BRCA polypeptides as the genes which are part of chromosomes 17 and 13, and function in the same way. In his view, this informational symmetry “dwarfs the significance of the structural differences” and does not remove the isolated DNA from the category of products of nature, thus precluding patent eligibility.
In other words, he characterized the isolated genes and the chromosomal DNA from which they are isolated in terms of their informational content rather than their chemical structures. The dissent included criticisms of the Myriad claims regarding claim breadth, issues that properly are considered under Section 112 of the patent statute.
The Supreme Court took Judge Bryson’s dissent and made it the basis of its decision, holding the isolated genes unpatentable under Section 101 of the patent statute. The opinion characterized the claimed invention as being the discovery of the information in the DNA, rather than the chemical isolation of the molecule that uses the “information” in the biochemical process of protein synthesis. The opinion states that “separating [a] gene from its surrounding genetic material is not an act of invention.”
In a key passage that goes to the heart of the Court’s opinion, the Court states, “Myriad’s claims [are not] saved by the fact that isolating DNA from the human genome severs chemical bonds and thereby creates a nonnaturally occurring molecule (emphasis added). 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.”
Rather, the Court concludes that Myriad’s invention is the discovery of the genetic information in the code embodied in the gene and present in both the natural and isolated DNA, therefore the identity of information renders the nonnatural molecule to be categorized as a product of nature and patent ineligible.
Myriad’s invention is not just the discovery of the location and sequence of the BRCA1 and BRCA2 genes that code for specific polypeptides, but their chemical isolation. To state that a claim for a DNA molecule is not a claim for a chemical composition is nonsense. It is a claim for a chain of nucleotide base pairs, a molecule whose utility resides in the genetic code embodied in the molecule. The molecule is admitted to be “nonnaturally occurring” and yet is called a product of nature!
To a chemist, this is incomprehensible, as Judge Lourie recognized and the other judges and justices could not.
If it should now be the law that patent eligibility of a molecule with a defined chemical structure, whether DNA or otherwise, is determined by whether or not the “information” in that structure is the same as the “information” in a related naturally occurring molecule, this has far-reaching implications. For example, if the “information” in an antibody is its antigen-binding specificity, then any antibody fragment that retains the same antigen-binding specificity would be patent ineligible. Similarly, if the “information” in an enzyme is its substrate specificity, then any portion of the enzyme molecule that retains the same substrate specificity and catalytic function would also be patent ineligible.
A hormone such as insulin, if modified by adding or deleting amino acids, but which retains the hormone’s function in controlling glucose levels would, by the Court’s new criterion, fail the test for patent eligibility.
The reductio ad absurdum of this principle renders thousands of chemical compositions unpatentable under Section 101 merely because they function in the same way as naturally occurring molecules from which they merely differ by the “noninventive” process of making and breaking of chemical bonds.
Chemistry, it would seem, is no longer a sophisticated science but a mere prosaic manipulation that, while not magic, is child’s play to one of ordinary skill in the art. Perhaps some Nobel prizes should now be revoked because their recipients merely made or broke chemical bonds to produce other molecules, apparently not activity for which great honor is warranted.
The Supreme Court’s decision has been widely touted as being a boon to research, especially for cancer patients, because of the high cost and limited availability of the patented test using the BRCA1 and BRCA2 genes.
A note of caution: Myriad spent years of effort and millions of dollars determining which portions of the approximately 80 million-base-pair-long chromosome 17 and the 114 million-base-pair-long chromosome 13 represent the portions coding for polypeptides that are found in people with a significantly higher likelihood to develop breast or ovarian cancer and not in those lacking that gene. It has attempted to recover this investment by patenting the isolated DNA used in its test for cancer vulnerability and charging a high price for the test. If other companies can now piggyback on that costly labor and charge a much lower price for the test, how many other companies will make similar investments and efforts if patent protection is now unavailable? Some companies will still do the research but may keep the results secret, resulting in wasted effort and resources by others trying to duplicate their achievements.
The patent system, requiring full disclosure in return for a limited period of exclusivity, was intended to avoid such waste and delay in making scientific progress in medicine and other disciplines. A patent on a new chemical composition must disclose how to make and use it. If this valuable information is kept secret, biochemical science is retarded and wasteful duplication takes the place of rapid advances.
I have been a professor of organic chemistry for nine years and a patent practitioner in the chemical, pharmaceutical, and biotechnological arts for 36. Judge Lourie’s opinion should have been adopted by the Supreme Court. I cannot accept a Supreme Court decision that trivializes chemistry and elevates biological ”information” over chemical structure in patent law, and that usurps the role of Congress and creates a new class of patent-ineligible subject matter by judicial fiat. I hope that other patent practitioners with chemical training, as well as other chemists, biochemists, and biotechnologists will agree.
Bernhard D. Saxe, Ph.D., J.D. ([email protected]), is a retired partner in the Washington, DC, office of Foley & Lardner. The opinions expressed herein are his alone and do not necessarily represent those of Foley & Lardner or its clients.