The following contribution to our gene patenting symposium comes from Kevin Noonan, a partner at McDonnell Boehnen Hulbert & Berghoff LLP.
It is one of the misfortunes of the human gene patenting debate that there has been precious little discussion of patent law (at least from those opposing gene patents). Admittedly, patent law is an arcane area of the law, and patent law discussions can be a bit dry. It has been much more fruitful to focus on issues that are, in truth, related to healthcare policy, or insurance, or the uneven distribution of health care among the states, or to introduce political prejudices about purported corporate ownership of human genes, or threats to personal integrity and autonomy. However important those issues may be, their solution lies outside the realm of patent law, and will not be solved by a decision that human genes should be ineligible for patent.
Concurrently, a number of myths have arisen, some out of ignorance and others because they serve their proponents’ political agenda and appeal to emotion rather than reason. But even a cursory look at these arguments show that they are baseless.
For example, claims to genes do not raise ownership issues for humans. It might have been excusable for Michael Crichton to make this error in a op-ed piece in The New York Times, but lawyers know better (provided they have read the Thirteenth Amendment recently).
Patenting isolated human DNA does not inhibit innovation, or necessarily even access to innovation. It is easy to forget today the basis for gene patenting in the past. Any number of biologic drugs have been developed that, according to a recent Federal Trade Commission report, “have improved medical treatments, reduced suffering, and saved the lives of many Americans.” These drugs were developed by companies that isolated the genes – including, but not limited to, erythropoietin, human growth hormone, interferon, blood clotting Factors VIII and XI, human insulin, tissue plasminogen activator – encoding them, because only by doing so could these therapeutically important proteins be produced in useful quantities. The patent incentive was instrumental in supporting investment in these companies, and in developing a biotechnology industry in the U.S. that has been a world leader for twenty-five years. As anyone following the debate on follow-on biologics will recognize, the need for patent protection to attract investment in what remains a fundamentally risky industry has not diminished.
Patenting isolated human DNA does not inhibit genetic research. There are more than eight thousand scientific research papers published on the BRCA genes since the grant dates of the patents. Even for-profit clinical testing can be performed in the face of these claims, based on the lack of any necessity to produce an isolated copy of the full-length sequence. As discussed above, large-scale sequencing can be performed without incurring patent infringement liability as to the isolated DNA claims.
There is no evidence that patenting isolated human DNA inhibits or will inhibit future technologies such as personalized medicine. As has been shown by multiple studies over the past ten years, in a variety of reports from the U.S., Germany, Australia and Japan, and despite sometimes Herculean efforts, there has been no finding that “patent thickets” or the “anticommons” have affected the research of academic scientists.
Patents are much more limited in scope than their detractors would have the public believe. A patent provides the patentee (for a limited time) with the right to exclude any unauthorized party from practicing an invention, and the scope of that right depends on the patent claims. Claims to “human genes” have a canonical form that has been developed over the thirty years during which “genes” (human or otherwise) have been patented under U.S. law:
An isolated nucleic acid having a nucleotide sequence that encodes a protein having an amino acid sequence identified by SEQ ID NO. X.
There are several limitations to this sort of claim that are relevant. First, what is claimed is a composition of matter, a molecule, that can be described by its sequence but is not the same as that sequence. In addition, the nucleic acid must be isolated from its biological source, which is generally recognized as having been either cleaved from genomic DNA or enzymatically synthesized (in a laboratory by a scientist) from cellular messenger RNA. This requirement stems, in part, from Diamond v. Chakrabarty, wherein the claimed DNA must show “the hand of man” and be “markedly different” from what occurs naturally. That standard was established during a time in which isolating a human gene was truly analogous to finding a needle in a haystack and the needle was made of hay. While not based on a “sweat of the brow” requirement, the necessity for the “hand of man” was more evident during those times than (perhaps) it is now, when the entirety of the human genome exists (representationally at least) in computer databases worldwide. Also, a DNA molecule was required to be isolated so that the claim would not encompass or “read on” the molecule as it exists in nature. This is not a question, necessarily, of patent eligibility, but rather of novelty; the gene in nature is not novel until it is isolated. This reasoning can be seen in early cases, such as the Wood-Paper Patent cases, and Cochrane v. Badische Anilin Soda Fabrik, where claims to compositions known in the prior art prevented patenting of the same or similar compositions despite their production using novel methods. The same rationale explains why isolated DNA claims cannot be read to encompass the genes in chromosomal DNA “isolated” from cells (but otherwise unchanged); because Frederich Mieschner “isolated” DNA to this level of purification in the 1880s, any such interpretation of the term “isolated” in isolated DNA claims would render them unpatentable for lack of novelty.
Second, the nucleic acid must have a sequence that encodes the full length of a particular protein; fragments of said sequence lie outside the scope of such claims because they do not encode the protein. This is required because the utility of such claims was to enable the isolated nucleic acid to be used to produce the encoded protein. The reason for this limitation stems from the purpose of such claims from the dawn of the biotechnology age: to be able to produce a protein having therapeutic or other beneficial uses. If an isolated gene was to be used to produce a therapeutic protein or any of the other patented human genes, it needed to be full-length or otherwise a truncated fragment would be produced that, even if it retained biological activity, could perhaps differ in biological half-life, immunogenicity, and numerous other important properties.
Finally, while the number of nucleic acid molecules encompassed by such claims may be large, they have one thing in common: they must encode the exact amino acid sequence set forth in the sequence listing (SEQ ID NO: X). Any deviation, however small, precludes literal infringement of the claim. This represents a compromise, because although the claim thus encompasses any nucleic acid that encodes a specific protein, the claim encompasses only those DNA molecules that have the specifically recited, identified sequence. Accordingly, literal infringement does not lie even if there are miniscule differences, such as a change from a valine to an isoleucine amino acid (a difference of a single methylene group, -CH2-) in a molecule having hundreds of amino acids. An important consequence is that these claims are far narrower than they may look, and “preempt” just what the patentee has disclosed.
The consequences of this construction affect the human gene patenting debate. First, the claims are only infringed if someone without authorization makes, uses, sells, offers to sell, or imports an isolated nucleic acid encoding the specified amino acid sequence. Typically, a “gene patent” identifies a cell or tissue source (and, frequently, identifies a plurality of cell or tissue sources as part of its characterization of a gene) that natively expresses the gene. Thus, anyone who uses such a cell or tissue source to study the gene without isolating it will not infringe. Second, portions of the gene can be isolated, sequenced, and characterized and not infringe; indeed, almost all modern methods for sequencing a gene depend on sequencing such fragments, whereby the full-length molecule is never produced, isolated, or used. Consequently, the methods do not infringe claims to human “genes” and thus have no effect on technologies like personalized medicine.
Third, the gene product (typically, a protein) can be isolated from the cell and studied without infringement, as can antibodies raised against the gene product. These antibodies can be used to detect under- or over-expression of the gene in cell or tissue sources for diagnostic purposes, and mutant forms of the gene product associated with disease can also be produced. All these activities do not infringe the gene claim. Fourth, because the sequence itself is not claimed (the isolated molecule comprising that sequence is), the sequence itself can be used for any purpose (including comparing an individual’s sequence with the gene as it occurs in healthy individuals or a sequence comprising disease-associated mutations) without infringing. For this reason, technologies such as “whole genome sequencing” and other present or future genetic diagnostic methods are unaffected by the isolated DNA claims and practice of these diagnostic methods do not infringe the DNA claims.
Properly understood, gene patenting does not impose undue burdens on the public. In fact, it is an important contributor to important societal benefits, such as better technology to provide better prevention and treatment for human diseases. These considerations have been largely ignored in the cacophony of policy arguments related to almost everything but whether patenting human genes actually promotes or inhibits progress. That is the basis for the constitutional mandate that supports Congressional power to grant patents in the first place, and that should be the standard. Thirty years of improvements in genetic diagnostics and gene-based (one way or the other) therapeutics should be enough to answer that question in the affirmative.