GENEWATCH
 
WHY GENES MUST REMAIN ELIGIBLE FOR PATENTING
By Kevin Noonan
 

In the gene patenting debate, as in war, truth has been the first casualty. Whether it's publicity campaigns by the American Civil Liberties Union with clever buttons declaring "Do not patent my genes" or hyperbolic rhetoric, polemic has quickly replaced integrity in an effort to influence public opinion (both at home and abroad).

A great deal of the anti-gene patenting argument is based on faulty premises, incorrect science, and a studied lack of appreciation of patent law as it has been applied, inter alia, to patent-eligibility for natural products. Since any rational debate is only as good as the information it is based upon, it is useful to address the more flagrant inaccuracies spouted by those who oppose gene patenting. Since "the truth shall set you free," there are some fundamental truths that must be considered when discussing gene patents. These include:

"Genes are a product of nature":  The facts

Patents claiming genes do not claim products of nature. The simple distinction is that gene claims recite that the genes are "isolated," and this limitation on their scope (as well as the 13th Amendment to the U.S. Constitution) prohibit the scenario that a patent holder may one day ring your doorbell and ask for a royalty from you because your liver is "using" a patented gene. More importantly, no one would want to own any individual person's genes: it has been known for more than forty years that any particular copy of a gene in an individual in a population is likely to contain at least one polymorphism that does or could (under the right environmental conditions) affect its function. Recent reports from J. Craig Venter on the complete sequence of human diploid genomic DNA (his own) detected more than 4 million nucleotide variants, including an extraordinary amount of genetic variation that could affect gene expression and gene products in unpredictable ways.

Moreover, and more significantly, human genes as they exist in human chromosomes are physically and chemically different from genes (really, isolated nucleic acids) as claimed in the overwhelming majority of so-called "gene patents." Genes have been described, properly, as the instructions for producing proteins. A gene encodes the amino acid sequence of a protein in a linear sequence of 3-base triplet codons that correspond in linear order to the amino acid sequence of the protein. However, in humans (and almost all other multicellular organisms) almost all genes are interrupted by "junk" DNA that does not encode protein (or at least does not encode the same protein that the gene encodes). The entire gene, junk and coding sequence, is transcribed into RNA by the cell and then the junk pieces are "spliced out," leaving the coding sequence (termed a messenger RNA or mRNA) that is used to produce the protein. Scientists take advantage of this process to clone genes, by isolating the mRNA and converting it into a DNA molecule called complementary DNA (cDNA), which is what is cloned, sequenced, and patented. cDNA does not exist in nature, and must be created by man using chemical and biological techniques. The hallmark of what the Supreme Court has declared is patent-eligible is "anything under the sun made by man." The cDNA copies of genes that form the basis for human gene patenting are "made by man" and not products of nature because they do not exist in nature prior to being synthesized in a test tube by a scientist. If we are honest in defining what are actually "products of nature," then they must by definition be produced by nature. cDNA molecules are not.

"Genes are products of nature":  The law

The legal argument that "products of nature" are not patent-eligible proves too much, because if genes are not patentable then many other natural products cannot be, either. This includes for example various antibiotics, and any number of products isolated from crude oil, plants, animals, and even humans. If genes are not patent-eligible, based on the fact that they are products of nature, then the patent incentive cannot exist for these "products of nature," either. If isolated human DNA is not patent-eligible, there is no principled reason why many other "natural products," such as antibodies, antibiotics, antisense and small interfering RNAs (siRNAs), hormones, metabolites, and proteins should be. Importantly, also included in any such "natural products" patenting ban would be biologic drugs, i.e., those drugs based on "naturally-occurring" human proteins. Indeed, proteins like human Blood Clotting Factors VIII and IX, insulin, human growth hormone, erythropoietin, tissue plasminogen activator, and all monoclonal antibodies are "isolated" in substantially homogeneous form, are structurally unchanged from their sources in blood and other bodily fluids, and are less altered than the cDNAs that are the subject of the claims to isolated human DNA invalidated by the district court. These considerations are also why the distinctions drawn in the Department of Justice's brief to the Federal Circuit is bad science, bad law and bad policy, in view of the expected importance of biologic drugs in the years to come.

There is no binding legal precedent that mandates that natural products are ineligible for patenting. On the contrary, the prevailing precedent, Diamond v. Chakrabarty, mandates patent eligibility to anything that is a "nonnaturally occurring manufacture or composition of matter - a product of human ingenuity,"  that is "not nature's handiwork, but [the inventors'] own." Isolated DNA (as well as these other examples of natural products) falls squarely within this rubric.

"Genes are part of a 'commons.'" 

Ironically, genes and gene patenting were originally assailed as creating a "tragedy of the anticommons," because private "ownership" thereof would impede genetic research. In fact, as has been shown by multiple studies over the past 10 years, gene patenting has done no such thing. Indeed, every report on the subject, whether from the United States1, Germany2, Australia3 or Japan4, has found that "patent thickets"5 or the "anticommons"6 rarely affects the research of academic scientists. In addition, the incentive for gene patenting motivated private companies, most notably Celera and Human Genome Sciences, to compete with the federally funded efforts to sequence the human genome. This competition accelerated these efforts and produced sequence information more rapidly than anyone expected. If these efforts provided genetic information that can be used to address human disease one day, one month, or one year earlier than it would have been produced otherwise, who can say the incentive is insufficient?

"Gene patenting inhibits genetic research."

In fact, a very good case can be made that the opposite is true. This is due to another distinction glossed over by those opposed to gene patenting: genetic information isn't patented (despite the district court's conceit that it could distinguish claimed DNA from other biological products for being "the physical embodiment of [genetic] information"). Patent law requires that claims be supported by a written description sufficient to enable the skilled worker to make and use the invention. For genes, this has meant that the genetic sequence is disclosed in almost all gene patents. This information can be used for any number of purposes, including sequence comparisons (which can be performed without "isolating" a gene), detecting genetic polymorphisms, and a variety of other scientific endeavors both before and after a patent grants, without risk of infringement.

Perhaps the best indicator that "inhibiting basic research" has not been a consequence of permitting patents on human genes is the extent to which basic research has been performed on the BRCA1 or BRCA2 genes, famously patented by the University of Utah and licensed by Myriad Genetics. The number of research reports in public databases reflecting ongoing basic scientific research in peer-reviewed scientific journals on these genes is almost 10,000: a simple database (PubMed) search of "brca1 or brca2" resulted in 7,855 publications. If either of the BRCA patents were to have had a chilling effect on basic research, the expectation would be that the number of scientific research reports would have declined in the face of patent infringement liability. On the contrary, the number of such publications has steadily increased each year, which is precisely what would be expected if these patents had no significant effect on basic scientific research.

What these patents do, of course, is prevent commercial activity-i.e., using the patented isolated human DNA or performing the patented methods for profit. This is a legitimate exercise of the patent grant.

"We don't need gene patents- researchers will do it anyway."

With regard to basic genetic research, this is true-it is the corollary to the previous point, that gene patents don't inhibit genetic research. However, there is a vast gap between identifying a genetic polymorphism related to a disease, or identifying a gene that encodes a useful protein, and developing a clinically validated test or producing a commercial biologic drug product, and that is where biotechnology companies come in. Of course, without the prospect of patent protection, investors are unlikely to provide the funding needed by start-up biotechnology companies to develop commercial embodiments of these inventions. And in view of the complexities of biotechnology products, other avenues-trade secrets and regulatory data exclusivity being just two-may enable companies to keep their "monopoly" much longer than the term of a gene patent. This would produce the kind of unfettered right in (undisclosed) genetic information that opponents of gene patenting wrongly assert exists today.

"Gene patenting inhibits 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 encoding them, including erythropoietin, human growth hormone, interferon, blood clotting Factors VIII and XI, human insulin, tissue plasminogen activator, and a host of others. 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 25 years. As anyone who followed 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. Patent policies abroad already permit those countries to "free-ride" on American innovation. Why should we adopt their failed policies here? And who will create the next generation of drugs based on biotechnology if we do?

Unfortunately, most of these arguments misconstrue the fundamental societal benefit conferred by the patent system-not incentives to innovate, and not even incentives to commercialize, but the requirements for disclosure that are fundamental to the patent grant. The plaintiffs fatally overreached in seeking to invalidate the patents-in-suit, and the U.S. District Court's decision, if upheld by the Federal Circuit or Supreme Court, is likely to have unintended and seriously negative consequences. The patents at issue, directed to isolated human DNA encoding BRCA1 and BRCA2, represent only the beginning of an era of personalized medicine that will be characterized by understanding, and utilizing, genetic differences that impact both an individual's propensity for succumbing to diseases and disorders as well as making a determination of the best therapeutic interventions and treatments for addressing them. Patents in this area are needed to promote expeditious disclosure of the genetic bases for such diagnostic and therapeutic approaches to human disease; without them, alternative means of protecting such discoveries, for example by holding them as trade secrets, will become more attractive. Patent-eligibility of isolated human DNA promotes not only disclosure of the DNA itself (and the proteins encoded thereby) but also the best mode for making and using the isolated human DNA and related methods. Even should the basic genetic information be available elsewhere, failure to patent also means failure to require full disclosure, and the attendant suppression of information would affect the development of reliable drugs and diagnostic methods (or worse, permit private companies to hold such information indefinitely). Such an outcome would be adverse to the public interest and contrary to the sound public policy underlying the Patent Act.

 

Kevin E. Noonan, PhD, JD, is a patent attorney and founder of patentdocs.org.

 

 

1. Walsh et al., 2003, "Science and the Law: Working Through the Patent Problem," Science 299: 1020).

2. Straus, 2002, Genetic Inventions, Intellectual Property Rights and Licensing Practices.

3. Nicol et al., 2003, Patents and Medical Biotechnology: An Empirical Analysis of Issues Facing the Australian Industry, Centre for Law & Genetics, Occasional Paper 6.

4. Nagaoka, 2006, "An Empirical Analysis of Patenting and Licensing Practice of Research Tools from Three Perspectives," presented in OECD Conference in Research Use of Patented Inventions, Madrid).

5. Shapiro, 2001, "Navigating the Patent Thicket: Cross Licenses, Patent Pools, and Standard Setting," In: Innovation Policy and the Economy 1: 119-50.

6. Heller & Eisenberg, 1998, "Can Patents Deter Innovation? The Anticommons in Biomedical Research," Science 280: 698-701.

 
 
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