Patent Law & Policy

Biotech patents - Gene-uine controversy.

When discussing the issue of patenting objects associated with the human body, the initial reaction among the general populace may be distaste. It seems unnatural and unethical that individuals be given ownership of something that occurs naturally. Biotech and DNA patents may elicit particularly strong reactions because genetic material built from DNA building blocks encodes who and what we are.

Although early patents on medical products of biotechnology, such as insulin, and early genetic engineering techniques have since expired, there is an expanding rate of new patent applications for novel processes and gene discoveries. One particular concern is that patents make the cost of genetic tests and genetic therapies unacceptably high by stifling competition, a concern demonstrated in the controversy over patenting the BRCA1 and BRCA2 genes associated with cancer. By detecting those genes, such as the genes that predispose women to breast cancer, doctors can offer preemptive treatment. There is one caveat: the gene is actually the property of a biotech company that has taken out a patent on it, even if a woman carries a copy of it naturally. This leads to a concern that gene patents may inhibit biomedical innovation by blocking scientists' access to genes and genetic materials that are essential to research. In this post, I will summarize the development of gene patents, the ethics of bio-medical patents, and the implications of the 2011 Myriad decision. Though the Association for Molecular Pathology v. U.S. Patent and Trademark Office ruling restores the status quo that existed for more than a decade after the U.S. Patent Office issued the patents to Myriad, the Federal Circuit's ruling does not help patients fighting cancer access these technologies, nor does it solve inherent problems in the system of patenting isolated genes.

Obtaining gene patents.

Patents for human genes are permitted if they can be distinguished from genes that occur naturally in the human body. To reach the bar for patentability in the U.S. an object or process must count as an invention, not a discovery, in addition to meeting further legal tests such as those for novelty, non-obviousness and usefulness.

Molecules, cells and even whole organisms are subject to patent protection if they represent a human innovation that is not found in nature. This has been true ever since the Supreme Court ruled in the leading biotech case Diamond v. Chakrabarty, 447 U.S. 303 (1980) where a lab-created bacterium that broke down crude was found to be patentable subject matter under 35 U.S.C. 101. The decision, written by U.S. Supreme Court Justice Burger, held that "Congress plainly contemplated that the patent laws would be given wide scope" and concluded that Congress had intended patentable subject matter to "include anything under the sun that is made by man." But human genes are discovered, not invented.

Background of Gene Patents

For the biotechnology industry, gene patents are the cornerstone of investment in research and development. Although the USPTO has granted patents on genes for over 20 years, the discretion of gene patenting continues to stir controversy. Some have questioned the ethics of monopolizing a resource that is basic to all living organisms. It has also been argued that patents unfairly restrict the use of genes, impeding both basic and commercial research. Though the genes are not patentable while they are in the body, genetic sequences that have been isolated, altered, or manipulated may receive patent protection.

Initially, patents were issued on whole genes with known functions. Inventors then began to seek patents on sequences of DNA, which focused on less than the entire gene. It became clear to researchers that future gene discoveries would be at the mercy of those who already held patents. In response, the USPTO published a revision to 35 U.S.C. 101 in. 2001:
If a patent application discloses only nucleic acid molecular structure for a newly discovered gene, and no utility for the claimed isolated gene, the claimed invention is not patentable. But when the inventor also discloses how to use the purified gene isolated from its natural state, the application satisfies the "utility" requirement. That is, where the application discloses a specific, substantial, and credible utility for the claimed isolated and purified gene, the isolated and purified gene composition may be patentable.
According to the revised guidelines, the USPTO sets the grounds for a utility requirement and states that a novel DNA sequence is patentable only if a demonstrable usefulness of the DNA sequence is disclosed in the application.

Ethical concerns
Opponents of gene patenting fear that permitting patents for DNA then turns human genes into commodities. Professor Suzanne Holland expresses this point when she comments that, "Biotechnology products are not widgets." She addresses a prevalent concern that gene patents may erode our dignity and personhood, since the end result allows the purchase and sale of human elements. Additionally, Professor Holland argues that these ownership rules as applied to the human body may result in a diminished commitment to human flourishing at the societal level.

However, these arguments fail to address the complexity involved in patent ownership: a patent does not necessarily confer legal ownership of anything. One can have a legal patent on an invention, but lack any legal rights to use that invention, let alone to license others to use or manufacture it. The only legal right conferred by a patent is the right to prevent others from using or possessing one's invention. Therefore, a patent on a human gene does not confer ownership of that gene, let alone ownership of all genes made according to the patent. Moreover, the concern that government endorsement of patents for genetic information reduces life to a commodity is arguably misguided and one-sided. While patenting DNA may run the risk of diminished human dignity, this trade-off may lead to an increase in human well-being. For decades, humans have manipulated the natural states of plant and animal species. The difference between these practices and the use of the current technology is that biotechnology makes it easier, and potentially more economical, for us to select preferred genetic traits.

It seems reasonable that a regulatory and legal framework like the one monitored and enforced by the USPTO in mechanical or electrical invention should give the same reward to biological advances. It controls incentives by properly keeping discovered items from receiving patent protection. However, the system in place today in the United States provides for almost unrestricted patenting of biomedical materials, which may be more industry-friendly than public interest oriented.

Myriad case

Last year, the United States District Court for the Southern District of New York shocked the American biotech industry by declaring Myriad's BRCA gene patents invalid. The striking decision in Association for Molecular Pathology v. US conflicted with practice in the United States for the past three decades, which maintained that genes, associated products, and methods are patentable. In July 2011, the Court of Appeals for the Federal Circuit reversed the district court's decision and affirmed the validity of Myriad's cancer screening claims.

The substantive questions posed by Myriad were as follows: Are genes patentable subject matter? How do gene patents impact medical research and health care? Do gene patents promote innovation as required by the Constitution?

Myriad sells a genetic test called BRAC Analysis, which detects mutations in two tumor suppressor genes called BRCA1 and BRCA2. Under normal conditions, these genes repair DNA that is damaged or help destroy the cell where DNA is unable to be fixed. Women with mutations in these genes are five times more likely to develop breast cancer during their lives. Many women with a history of breast and ovarian cancer in their families opt to undergo genetic testing to determine if they have the mutations on their BRCA genes that put them at increased risk for these diseases. This information is critical in helping these women decide on a plan of treatment or prevention.

The Plaintiff's argument hinged on whether DNA is that is isolated from the chromosomes is statutory subject matter or whether it is the product of nature. Myriad is the exclusive licensee of the family of patents relating to these isolated genes and genes sequences. As a result, the company controls all sequencing of the BRCA genes as well as the diagnostic testing for the BRCA mutations. However, Myriad refuses to grant any licenses for second-opinion BRCA testing. The limited research licenses it has granted are restrictive and often prevent patients from disclosing their test results to independent agencies to double-check results.
In the Federal Circuit, Myriad argued that patents allow companies time to recover their sizable R&D investments necessary for such advancements. If companies are not able to patent their technologies, Myriad contends, then there is no incentive to invest in medical research, and progress will suffer overall. Patents for tests, such as the one held by Myriad, give companies a monopoly on a critical diagnostic test, allowing them to charge the monopolistic prices necessary to recoup such large investments.

With three judges writing the decision and voting 2-1, we were left with three different opinions. The majority and concurring opinions gave great weight to the Patent Office's long-standing position that isolated genes are patentable. Judge Alan D. Lourie (who earned a PhD in chemistry), writing for the Circuit, reasoned that the isolated BRCA gene was chemically different from the gene in its naturally occurring state. Similarly, Myriad's patient screening included enough transformation to be patent-eligible. Judge Lourie summarized more than a century of cases dealing with all kinds of substances with natural precursors or analogs. He concluded that the test was whether the claimed substances were "markedly different - have a distinctive chemical identity and nature" - from the naturally occurring version. The court held that the BRCA gene as it appears in nature was not the same as the BRCA gene as separated by Myriad. Although the exact peptide sequence was present in both instances, the two molecules were chemically different compositions. The court cited the PTO's long-standing policy in favor of the patentability of isolated DNA and other natural products.

Judge Kimberly A. Moore (who earned her degree in electrical engineering) agreed with Judge Lourie that the plaintiffs had standing to fight Myriad's patent in court and that most of Myriad's patents were valid. However, her decision focused on the new utility the isolated DNA would have and her analysis stated that the different chemical nature of the isolated DNA was not the sole material factor to be considered in determining the validity of Myriad's patents.

Implications for commercialization and patients

Since Myriad was the sole provider of the BRCA tests, the opportunity for others to offer the tests could harm patients. Patients cannot have their test results confirmed by independent
companies, and the tests were offered only at monopoly prices, so there were many claimants that could not afford the test.

Myriad argued that gene patents were necessary to incentivize research. Such patents made commercial profits possible, and potential financial rewards drove research. On the other hand, such patents have the potential to limit patient access to tests and stifle research. Existing gene patents would likely not incentivize researchers to explore and study portions of the genome that were already claimed, as expensive licensing fees would be another hurdle.

Potential solutions and future of Myriad

The latest round of the Myriad decision does not harmonize the plain language of Section 101 of the Patent Act and the Constitutional mandate to promote progress of the useful arts. The Constitutional mandate to promote progress should include balancing any grant of exclusive rights against providing access. Patenting isolated genes and gene sequences can limit access to research for the duration of the patent. Categorizing these genes as chemically different despite their biological equivalence is gaming the system. This interferes with progress and is therefore in direct violation rights empowering Congress to grant exclusive rights, such as patents and copyrights, for "limited timed times to promote Progress of Science and the Useful Arts."
In terms of patent litigation, if genetic patents hold up in court, third-party research by those who do not hold patents would be restricted. On the other hand, if gene patenting were voided, then the company that invested resources and time into research would not benefit financially. A solution that adheres to the patent rights system and also enables commercialization of affordably priced genetic diagnostic tests that physicians seek will make the best possible diagnoses and treatment plans for their patients.
One such potential solution to balance private interest and public desires to achieve treatments would involve the creation of an independent, non-profit body that would serve as an independent agency for human gene patents. Rights holders could license their patents to the patent pool, where aggregation may be permitted. Such a system may lower the barriers to entry and ensure that monopolies do not prevent inventors from being shut out. Alternatively, limited use patents may provide some financial profits for research companies without severely impacting scientific research.

Commentators of the Myriad decision believe that this long debate will continue for years to come and the case is likely heading to the Supreme Court. Whichever way the court ultimately comes out on this issue, whether following the broader precedent of the Diamond case or narrowing their scope in light of the lower court's reasoning, patenting human genes should be permissible but closely regulated to ensure a balance between the conflicting interests of information sharing while protecting company's hefty investments. Genes offer opportunities for new scientific discoveries, and restricting the barriers of gene patents may open up new progress on this front.

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