Revisiting the USPTO's Examination Guidelines for Gene Patents: Congressional Inaction, USPTO Restraint, and Judicial Remedy

BackgroundThe patenting of human genes has been the subject of debate for decades. While China has gradually come to play an important role in the global genomics-based testing and treatment market, little is known about Chinese scholars’ perspectives on patent protection for human genes.MethodsA content analysis of academic literature was conducted to identify Chinese scholars’ concerns regarding gene patents, including benefits and risks of patenting human genes, attitudes that researchers hold towards gene patenting, and any legal and policy recommendations offered for the gene patent regime in China.Results57.2% of articles were written by law professors, but scholars from health sciences, liberal arts, and ethics also participated in discussions on gene patent issues. While discussions of benefits and risks were relatively balanced in the articles, 63.5% of the articles favored gene patenting in general and, of the articles (n = 41) that explored gene patents in the Chinese context, 90.2% supported patent protections for human genes in China. The patentability of human genes was discussed in 33 articles, and 75.8% of these articles reached the conclusion that human genes are patentable.ConclusionChinese scholars view the patent regime as an important legal tool to protect the interests of inventors and inventions as well as the genetic resources of China. As such, many scholars support a gene patent system in China. These attitudes towards gene patents remain unchanged following the court ruling in the Myriad case in 2013, but arguments have been raised about the scope of gene patents, in particular that the increasing numbers of gene patents may negatively impact public health in China.

Patenting human genes: The myriad controversy

Recent court hearings and legislation proposals regarding biotechnology and biotechnological methods have proven to be unfavorable to several avenues of scientific research and innovation. There exists a tension between interests of the scientific community and the means through which legislation permits scientists to realize those interests. Factors larger than those of the scientific community must be taken into account when penning policy, and the same holds true for any interpretation by judiciary bodies. The presence of a strain between advocacy for the scientific community and objectiveness in order to allocate the products of scientific innovation permeates legislative decision-making. In recent years, it appears as though advocacy for private scientific innovation has decreased as issues surrounding distributive justice have increased. There has been a tightening of the reigns by the United States Supreme Court regarding patent cases involving biotechnology over the past few years. With landmark cases such as Prometheus v. Mayo (2012) and AMP v. Myriad Genetics (2013) there appears to be a trend of judicial precedence that is unfavorable to scientific innovation.[1] In Prometheus v. Mayo, the court ruled that a patent is ineligible if it is deemed to be applying the laws of nature using conventional methods known to the field. In AMP v. Myriad Genetics, the court ruled that isolated human DNA was not patent-eligible, without applying existing case law, relaying that DNA is both “unique” in its own right, and a “physical embodiment of laws of nature” and therefore cannot be patented.[2] Both court decisions were deemed unfavorable by the scientific community. The current dispute over priority filing, scope of claim, and patent-eligibility of CRISPR/Cas9 technology[3] will be a critical determination that will likely have adverse legal consequences for the relationship between patent application, litigation, and scientific innovation. The complexity of the bureaucratic process in which patents are granted (through the US Patent and Trademark Office) leaves much room for error. The factors driving the discrepancies in the patent granting process are no doubt multifaceted, but the influx of patent applications and the limited resources of the patent office create a perfect storm for the spike in patent litigation cases filed within the past decade.[4] In addition, court rulings, such as the Myriad decision, have left many members of the scientific community confused. The verdict in Myriadmisunderstands what scientific innovation is and as a result creates a tremendous gray area in which scientists have to be mindful of the law, thereby ignoring the reality of scientific innovation. Patents assist scientific innovation due to their allowance of a government-granted monopoly for an extended period of time. However, considerations over the patentability of various prognostic and diagnostic methods may be considered an impediment to public health, precisely because of this monopoly. I assume that one (of many) purposes of policy is to allocate resources, in which case there is a delicate push and pull that occurs between private profits obtained from scientific innovation and public access to novel pharmaceuticals and biologics. While I do believe that the development of private enterprise is a critical component of driving scientific innovation, public access needs to be an equally important consideration. In preceding decades, the former has been granted greater weight, thereby detracting from the latter. These policy implications illustrate larger issues and trends in statutory law. One major piece of legislation that recently passed and has questionable implications for the scientific community is the Biologics Price Competition and Innovation Act of 2009 (“Biosimilars Act”). It passed with the intention of promoting innovation of biologics and lowering their price, thereby increasing accessibility to the wider population. The Biosimilars Act is highly analogous to the Hatch-Waxman Act of 1984, which skyrocketed the production of generic drugs and tremendously lowered the price of small molecule drugs.[5] However, controversy exists over whether or not this is a realistic endeavor, given the scientific reality of the nature of biologics and the twelve-year exclusivity granted to innovator companies. The discrepancy between intention and outcome in the Biosimilars Act is speculative, but may be attributed to the lack of competition faced by biologic innovator companies. The discontinuity between policymaking, court interpretation, and their implications for scientific innovation that has emerged in recent years appears to be far from over. In fact, it is likely that such trends may lead to a battle between scientific innovation, legislation, and legal jurisdiction. The discontinuity also indicates that there is a delicate balance between the ability of self-regulation in the private sphere to promote scientific innovation and the oversight of government in its ability to properly allocate the products constructed from scientific progress.

Patents prevent anyone but the patent-holder from manufacturing, using, or distributing discoveries and inventions for twenty years from the date of filing. In order to be patentable, an invention needs to be useful, non-obvious, and represent an original design or process rather than an abstract concept or item commonly found in nature. Patents related to genetics received their first legal test in 1980, when the U.S. Patent and Trademark Office (USPTO) granted protection to a genetically engineered bacterium that consumed oil and was useful in cleaning oil spills. The legality of this patent was affirmed in Diamond v. Chakrabarty, where the Supreme Court observed that although “[t]he laws of nature, physical phenomena, and abstract ideas” were not patentable subject matter under § 101, the claimed invention in the case was distinguished from nature as “a product of human ingenuity having a distinctive name, character and use.” The Court held that although the invention comprised a living thing, the patentee had produced a new bacterium with “markedly different characteristics” from the original. The bacterium was, therefore, “not nature’s handiwork but [the patentee’s] own.” Although Chakrabarty settled the question of whether manufactured genes can receive patent protection, it did not address the patentability of naturally occurring genes. In the absence of such definitive legal guidance, the USPTO routinely issues patents on human deoxyribonucleic acid (DNA) sequences, reasoning that the material has been purified from its natural form through human intervention and is thus sufficiently “touched by man” to be beyond the scope of nature. From 1980 to 2009, the USPTO issued between 3,000 and 5,000 patents on human genes, encompassing nearly 20% of the human genome. In addition, the USPTO has issued nearly 50,000 patents involving human genetic material, yet the fundamental validity of such patents has never been reviewed until now. In March 2010, a district court decision in New York brought attention to the role of gene patents in the advancement of biomedical research. In Association for Molecular Pathology v. United States Patent and Trademark Office (“AMP”), the Southern District of New York enforced a strict standard for subject matter patentability by invalidating seven patents relating to the human breast cancer genes BRCA1 and BRCA2 (collectively “BRCA”). The court reasoned that not only were the coding sequences and mutations of BRCA results of natural phenomena but that, the purified forms of BRCA maintain essentially the same structures and functions as their natural forms and therefore fall outside the scope of patent law protection. Although the decision primarily addressed the patent’s subject matter, the court also noted the possible social implications resulting from how patents affect access and innovation in biomedical research. Contrary to concerns raised by the plaintiffs in AMP, empirical studies indicate that gene patents do not impede access to biomedical research data or play a significant role in influencing the topics of research that scientists choose to pursue. These results suggest that while gene patents do not impede innovation, they may not be necessary for it either, at least at the foundational level. Some scholars still maintain, however, that patent protection is necessary to ensure adequate funding for further research, development, and marketing of their innovations. This Note focuses on the role of patent law in encouraging or discouraging innovation in the field of biomedical research. Specifically, this Note analyzes the policy justifications underlying gene patents and explores whether these justifications validly apply to the patenting of the BRCA gene. Part I establishes a basic understanding of patents, genes, and gene patents. Part II provides greater detail regarding the arguments and holding in the AMP case. Part III introduces the traditional rationales for patent protection and applies them to gene patents. Part IV considers the concerns surrounding gene patents and whether these concerns are realistic given the results of empirical studies on the relationship between patents and biomedical research. Part IV also examines whether the district court’s holding in AMP is consistent with the policy goals behind intellectual property rights and the reality of the industry. Finally, this Note concludes that, in general, patents do not impede upon innovation. However, the broad issuance of composition claims, such as those held by Myriad in AMP, may block research in areas of study that the patent holder is not pursuing (such as therapeutics). This Note suggests that this issue could be resolved by narrowing the focus of the patent claim to the application of the gene composition, rather than the composition on its own.

An increasing number of international research and governmental institutions are challenging several gene patents, arguing that the patent holders’ absolute control of diagnostic methods is not in the public's best interests. Most notably, the Institut Curie, a cancer research centre in Paris, is leading the fight against Myriad Genetics, a US biotechnology company that plans to install a monopoly on all genetic work associated with the breast and ovarian cancer predisposition gene brca1 . The critics of Myriad's wide‐ranging patent rights maintain that the company's absolute control not only prohibits further research on the diagnosis of and therapies against breast cancer, but also has a detrimental effect on public health. Physician examining mammographs. ![][1] > Critics of Myriad's wide‐ranging patent rights maintain that it not only prohibits further research on diagnostics and therapies but also has a detrimental effect on public health Since the European Commission adopted a directive allowing human genes to be patented in July 1998, many such patents have been granted and indeed challenged, including the battles over the insulin, relaxin and hematopoietin genes. In 2001, seven years after Myriad Genetics first identified the sequence of brca1 , the European Patent Office (EPO) granted the company three patents covering all potential diagnostic and therapeutic applications based on the gene's sequence. Several European research centres and associations quickly contested the first two patents in an attempt to fight Myriad's monopoly. More recently, in August 2002, the Institut Curie, the Institut Gustave‐Roussy, the Assistance‐Publique‐Hopitaux de Paris together with almost all European genetics societies and many scientific institutions and governments turned up the heat and filed a joint opposition notice to the third patent. As this protects the isolated gene and the corresponding protein, and includes all imaginable future therapeutic uses, such as gene therapy and screening of drugs or transgenic animals, … [1]: /embed/graphic-1.gif

Seeing the Forest Through the Trees: Gene Patents & the Reality of the Commons

Gene patents form the intellectual property platform for companies to translate biomedical research into life-saving therapeutic and diagnostic agents. These patents are also controversial, with critics charging that gene patents are unjustified, and they substantially impede research and access to genetic diagnostic testing. Myriad Genetics, the exclusive licensee of patents relating to the BRCA breast cancer susceptibility genes, has been a lightning rod for much of the negative commentary on gene patents. The criticism has culminated in a lawsuit by the ACLU challenging the patent eligibility of Myriad’s gene patents, and by implication the eligibility of gene patents in general. On March 29, 2010, the district court ruled in favor of the ACLU, invalidating all of the challenged patent claims for encompassing subject matter ineligible for protection under Section 101 of the patent statute. As of November 2010 the case is at the Court of Appeals for the Federal Circuit, and thus the status of gene patents is still very much in play. This chapter explains what a gene patent is, and discusses the legal doctrine supporting the USPTO’s position that gene patents are valid. It also considers the societal costs and benefits of gene patents, their role in biotechnology research and development, and the ACLU’s challenge to Myriad’s patents. It explain why many of Myriad’s patent claims challenged by the ACLU for impeding BRCA genetic testing are likely invalid for lack of novelty or obviousness, or not infringed by BRCA testing as currently performed. It explains why the human gene patent thicket has for the most part failed to materialize, particularly with respect to basic research and the use of DNA hybridization arrays. It concludes with suggestions for more appropriate and measured alternatives to the doctrine of patent eligibility for reining in truly unworthy gene patents.

Will Gene Patents Impede Whole Genome Sequencing?: Deconstructing the Myth that Twenty Percent of the Human Genome is Patented

HIGHLIGHTS Increase in the number of agribusiness biotechnology patents. Development of science, technology and innovation in the context of measuring economic growth. Increase in the number of patents and better results in agricultural productivity in the field.

An exorbitant monopoly: the High Court of Australia, Myriad Genetics, and gene patents

Modern biotechnological advances have posed new challenges before the existing patent laws of countries as biotechnological inventions differ markedly from chemical and mechanical inventions that have been the traditional subject matter of patents. With the development of human genomics and success of the Human Genome Project, the gene becomes more important because of its informational content rather than its material qualities (physical attributes). Patent is a subject primarily concerned with questions inside a jurisdiction. Although the adoption and ratification of trade-related aspects of intellectual property rights (TRIPS) has brought a unified character to patent laws of member countries of the World Trade Organization (WTO) to a certain extent, these countries have adopted different approaches regarding biotechnology patents in tune with their national policies. As a result, the scope and coverage of biotechnology patents vary from country to country. Even in countries having similar patent laws such as the USA and Canada, interpretations of such laws by courts vary significantly. These variations among countries are important for the proper understanding of the trends in biotech patents. Therefore, the present chapter makes a comparative study of patent laws and practices relating to biotechnology patents in the USA, Canada, European Union and India in order to collate the common issues and the differences among and between them. The USA being a pioneer in biotechnology research exerts great influence upon other countries; the European Union reflects the unified approach of different member states in a politically diversified system; Canada makes a distinction between patenting of higher life forms and lower life forms and India represents the concerns of developing countries.

Over the past few decades, scientific researchers have come under increasing pressure to commercialise their findings. This pressure and an increase in academic–industry connections have raised a number of concerns, including a potential loss of funding for basic science, the increased likelihood of researchers and universities finding themselves in (real or perceived) conflicts of interest and a potential loss of public support for research. In the human genetic research context, additional concerns have been raised including the legality of gene patents and their effect on innovation, the potentially premature marketing of genetic technologies and the readiness of health‐care systems, physicians and society for the increasing number and range of genetic testing options. While some of these concerns have proven less worrisome than others, the full extent of the impact of commercialisation of human genetic research is not yet known and there is much room for further research in this area. Key Concepts Commercialisation of scientific research can essentially be understood as the conversion of research findings into a commercial product or service (Downie and Herder, 2007) and can involve industry–university partnerships, patenting of research findings or spin‐off companies created as a result of research. Commercialisation of scientific research has grown significantly in recent years and is increasingly being prioritised by public funding bodies. As a result, the scientific community is under pressure to demonstrate the commercial value of their work. This is often referred to as ‘commercialisation pressure’. In the genetic research context, gene patenting has raised a lot of controversy in terms of its moral, ethical and legal validity. The legality of these patents has been debated around the world, and different jurisdictions appear to be coming to different conclusions on this issue. One concern that is frequently raised regarding gene patenting is its potential to negatively impact innovation by creating an ‘anticommons’ (Heller and Eisenberg, 1998). The ‘anticommons’ concern is essentially the idea that the growth of intellectual property protection will hinder researchers from accessing necessary research inputs, thereby slowing scientific progress and innovation. This concern has received a great deal of attention; however, recent research raises questions about the extent to which this concern has actually manifested. There has also been a lot of ‘hype’ surrounding genetic research, which has frequently been portrayed to the public in an overly optimistic manner in terms of its potential benefits and timelines in which these benefits are likely to materialise. This phenomenon is not necessarily the result of any intention to mislead the public but rather the product of many different pressures and incentive structures that scientists, research institutions and the media are operating under. Direct‐to‐consumer genetic testing has also raised concerns in terms of the marketing strategies employed by companies offering these tests and their ability to actually deliver useful health information to consumers. As a result, some regulatory bodies are taking a firm stand against companies marketing these tests, while others appear to be taking a more permissive stance.

For more than a decade, gene patents have been the driving force behind the burgeoning American biotechnology industry. Many people—even otherwise sophisticated lawyers—assume that such patents cover only methods and therapeutic applications. They are shocked to learn that patents on genes themselves, as long as they are isolated from the body, are routinely allowed by the United States Patent and Trademark Office and acquiesced in by the courts. The practical consequences of this development are equally startling to the non‐patent community: gene patent holders can control not only commercial applications, but virtually all research involving the subject genes. Since genes are valuable as transmitters of information, the ultimate effect can be a monopoly on the use of that information. This, we believe, takes intellectual property protection to an unprecedented level. All challenges to gene patents in the United States have thus far been dismissed almost out of hand. One possible avenue of attack that has gotten little attention involves the ‘product of nature’ doctrine, whose roots in American patent law go back to the nineteenth century. In its strongest form, it holds that compounds and compositions of matter that are not materially different from naturally occurring products are not patentable subject matter. In this article, we explore the history and current status of this doctrine. After reviewing some of the critical scientific elements of gene patents, we ask whether the product of nature doctrine, properly argued, might be reinvigorated as a brake on the rush to patenting the human genome. We believe that it would be particularly useful for lawyers and regulators in Europe to examine the American experience, since the European position on gene patents seems still to be more open to debate.

In this paper, we point out three possible ways gene patents could impede scientific research. First, gene patent laws might exacerbate the culture of secrecy ubiquitous in science. Second, gene patents may limit researchers’ ability to study poly or multigenic diseases without access to all genetic etiologies. Third, gene patents could result in a “patent thicket”.

Invented here but owned elsewhere: The widening gap between domestic and foreign patent ownership in Canada