The Myriad Decision at 10.

A decade ago, the US Supreme Court decided Association for Molecular Pathology v. Myriad Genetics, Inc., concluding that isolated genes were not patentable subject matter. Beyond being a mere patent dispute, the case was a political and cultural phenomenon, viewed as a harbinger for the health of the biotechnology industry. With a decade of perspective, though, Myriad's impact seems much narrower. The law surrounding patentable subject matter-while greatly transformed-only centered on Myriad in small part. The case had only a modest impact on patenting practices both in and outside the United States. And persistent efforts to legislatively overturn the decision have not borne fruit. The significance of Myriad thus remains, even a decade later, hidden by larger developments in science and law that have occurred since the case was decided.Expected final online publication date for the Annual Review of Genomics and Human Genetics, Volume 25 is August 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Ethical, legal, and social issues in the Earth BioGenome Project.

The Earth BioGenome Project (EBP) is an audacious endeavor to obtain whole-genome sequences of representatives from all eukaryotic species on Earth. In addition to the project's technical and organizational challenges, it also faces complicated ethical, legal, and social issues. This paper, from members of the EBP's Ethical, Legal, and Social Issues (ELSI) Committee, catalogs these ELSI concerns arising from EBP. These include legal issues, such as sample collection and permitting; the applicability of international treaties, such as the Convention on Biological Diversity and the Nagoya Protocol; intellectual property; sample accessioning; and biosecurity and ethical issues, such as sampling from the territories of Indigenous peoples and local communities, the protection of endangered species, and cross-border collections, among several others. We also comment on the intersection of digital sequence information and data rights. More broadly, this list of ethical, legal, and social issues for large-scale genomic sequencing projects may be useful in the consideration of ethical frameworks for future projects. While we do not-and cannot-provide simple, overarching solutions for all the issues raised here, we conclude our perspective by beginning to chart a path forward for EBP's work.

Preprint servers and patent prior art: Preprints can jeopardize the patentability of an invention: Preprints can jeopardize the patentability of an invention.

Posting papers on preprint servers creates patent 'prior art' and is likely to affect the patentability of any underlying invention.

Models of Technology Transfer for Genome-Editing Technologies.

Many of the fundamental inventions of genome editing, including meganucleases, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPR, were first made at universities and patented to encourage commercial development. This gave rise to a diversity of technology transfer models but also conflicts among them. Against a broader historical and policy backdrop of university patenting and special challenges concerning research tools, we review the patent estates of genome editing and the diversity of technology transfer models employed to commercialize them, including deposit in the public domain, open access contracts, material transfer agreements, nonexclusive and exclusive licenses, surrogate licenses, and aggregated licenses. Advantages are found in this diversity, allowing experimentation and competition that we characterize as a federalism model of technology transfer. A notable feature of genome editing has been the rise and success of third-party licensing intermediaries. At the same time, the rapid pace of development of genome-editing technology is likely to erode the importance of patent estates and licensing regimes and may mitigate the effect of overly broad patents, giving rise to new substitutes to effectuate commercialization.

The History of Patenting Genetic Material.

The US Supreme Court's recent decision in Association for Molecular Pathology v. Myriad Genetics, Inc. declared, for the first time, that isolated human genes cannot be patented. Many have wondered how genes were ever the subjects of patents. The answer lies in a nuanced understanding of both legal and scientific history. Since the early twentieth century, "products of nature" were not eligible to be patented unless they were "isolated and purified" from their surrounding environment. As molecular biology advanced, and the capability to isolate genes both physically and by sequence came to fruition, researchers (and patent offices) began to apply patent-law logic to genes themselves. These patents, along with other biological patents, generated substantial social and political criticism. Myriad Genetics, a company with patents on BRCA1 and BRCA2, two genes critical to assessing early-onset breast and ovarian cancer risk, and with a particularly controversial business approach, became the antagonist in an ultimately successful campaign to overturn gene patents in court. Despite Myriad's defeat, some questions concerning the rights to monopolize genetic information remain. The history leading to that defeat may be relevant to these future issues.

FAMILIAL SEARCHES, THE FOURTH AMENDMENT, AND GENOMIC CONTROL.

In recent years, police have increasingly made use of consumer genomic databases to solve a variety of crimes, from long-cold serial killings to assaults. They do so frequently without judicial oversight per the Fourth Amendment's warrant requirement by using consumer genomic platforms, which store hundreds of thousands or millions of user genomic profiles and enable law enforcement to infer the identity of distant genomic relatives who may be criminal suspects. This Essay puts this practice into context given recent legal and technological developments. As for the law, the Supreme Court in United States v. Carpenter has suggested that technologically driven and expansive datasets may be entitled to the full suite of Fourth Amendment protections. As for technology, we describe here the development of a novel technology that allows users to engage in genomic analysis in a secured environment without making such information available to a third party. Taken together, we present a possible technological solution to ensuring Fourth Amendment protections for direct-to-consumer genomic data.

Fortune and hindsight: gene patents' muted effect on medical practice.

Introduction: Physicians have long worried about gene patents' potential to restrict their medical practices. Fortune and hindsight have proven these worries exaggerated both in the UK and elsewhere. Neither current nor future medical practices appear to be impinged by gene patents, although they may be subject to future intellectual property disputes. Sources of data: Qualitative and quantitative (survey) studies of gene patents' effects on medical practice; recent developments in patent law. Areas of agreement: Traditional gene patents do not appear to have restricted medical practice in the UK, although their effect elsewhere has been more nuanced. Areas of controversy: Whether patents will restrict the spread of newer medical technologies is unresolved. Areas timely for developing research: Continuing survey data on practitioners' views concerning patents' role in the distribution of newer technologies would be beneficial.

Regulating Direct-to-Consumer Polygenic Risk Scores.

This Viewpoint discusses the possible harms associated with direct-to-consumer polygenic risk scores and advocates for federal regulation.

Assessing-and Extending-California's Insulin Manufacturing Initiative.

This Viewpoint reviews California's recently proposed CalRx initiative to manufacture biosimilar insulin, highlights challenges facing the initiative, and suggests ways in which, if successful, the initiative could serve as a model for state-managed development of drugs other than insulin, reduce drug prices, and provide other benefits.

CRISPR, Patents, and the Public Health.

Patent issues surrounding CRISPR, the revolutionary genetic editing technology, may have important implications for the public health. Patents maintain high prices for novel therapies, limiting patient access. Relatedly, insurance coverage for expensive therapies is waning. Patents also misallocate research and development resources to profitable disease indications rather than those that necessarily impinge on the public health. And it is unclear how CRISPR therapies will figure into the current regulatory framework for biosimilars. Policy makers and physicians should consider these issues now, before CRISPR therapies become widely adopted-and entrenched-in the marketplace.

Patent Law's Reproducibility Paradox.

Clinical research faces a reproducibility crisis. Many recent clinical and preclinical studies appear to be irreproducible--their results cannot be verified by outside researchers. This is problematic for not only scientific reasons but also legal ones: patents grounded in irreproducible research appear to fail their constitutional bargain of property rights in exchange for working disclosures of inventions. The culprit is likely patent law's doctrine of enablement. Although the doctrine requires patents to enable others to make and use their claimed inventions, current difficulties in applying the doctrine hamper or even actively dissuade reproducible data in patents. This Article assesses the difficulties in reconciling these basic goals of scientific research and patent law. More concretely, it provides several examples of irreproducibility in patents on blockbuster drugs--Prempro, Xigris, Plavix, and Avastin--and discusses some of the social costs of the misalignment between good clinical practice and patent doctrine. Ultimately, this analysis illuminates several current debates concerning innovation policy. It strongly suggests that a proper conception of enablement should take into account after-arising evidence. It also sheds light on the true purpose--and limits--of patent disclosure. And lastly, it untangles the doctrines of enablement and utility.

Immaculate Conception? Priority and Invention in the CRISPR Patent Dispute.

The U.S. Patent Trial and Appeal Board (PTAB), in an interference proceeding decided in February 2022, concluded that researchers at the Broad Institute (Cambridge, MA) were the first to "conceive" of using single-guide RNA CRISPR-Cas9 genome editing in eukaryotic cells in 2012. The PTAB reached this verdict even though competing researchers at the University of California, Berkeley, among other institutions, could document the idea 7 months earlier. Understanding the basis for the PTAB's decision turns on patent law's particular "conception" requirement. In this study, I explain that requirement, detail the PTAB's interference decision, and discuss the decision's practical effects on CRISPR technology and routine science.

Handle with Care: The WHO Report on Human Genome Editing.

The World Health Organization's recent Report on Human Genome Editing departs from similar reports from other institutions in that it recognizes that ethical assessments of the technology are deeply complex, surprisingly fragile, and subject to practical and political considerations. The WHO report largely recommends that human genome editing, rather than being accepted in some circumstances and banned in others, should be handled with care. The report recommends some oversight mechanisms-such as intellectual property licensing-previously undiscussed or underexplored in sister reports, and it recognizes that others-like international law-may be impractical. This essay explores how the report has shifted global considerations of governing human genome editing to more pragmatic ends.

Governance Choices of Genome Editing Patents.

There are a variety of governance mechanisms concerning the ownership and use of patents. These include government licenses, compulsory licenses, march-in rights for inventions created with federal funding, government use rights, enforcement restrictions, subject-matter restrictions, and a host of private governance regimes. Each has been discussed in various contexts by scholars and policymakers and some, in some degree, have been employed in different cases at different times. But scholars have yet to explore how each of these choices are subject to-or removed from-democratic control. Assessing the range of democratic implications of these patent governance choices is important in understanding the social and political implications of controversial or wide-ranging technologies because their use has a significant potential to affect the polity. This paper seeks to unpack these concerns for genome editing, such as CRISPR, specifically. Patents covering genome editing make an interesting case because, to date, it appears that the polity is concerned less with certain kinds of access, and more with distribution and limits on the technology's particular uses, such as human enhancement and certain agricultural and environmental applications. Here, we explore what it means for patents to be democratic or non-democratically governed and, in so doing, identify that patents covering many of the most controversial applications-that is, ones most likely to gain public attention-are effectively controlled by either non- or anti-democratic institutions, namely, private restrictions on licensing. This may be effective-for now-but lawmakers should be wary that such restrictions could rapidly reverse themselves. Meanwhile, other choices, like compulsory licenses, more broadly touch on democratic deliberation but, as currently structured, are aimed poorly for particular applications. Insofar as the public wants, or perhaps deserves, a say in the distribution and limits of these applications, illuminating the ways in which these governance choices intersect-or fail to intersect-with democratic institutions is critical. We offer some concluding thoughts about the nature of patents and their relationship with democratic governance as distributed claims to authority, and suggest areas for scholars and policymakers to pay close attention to as the genome editing patent landscape develops.

Biological controls for standardization and interpretation of adaptive immune receptor repertoire profiling.

Use of adaptive immune receptor repertoire sequencing (AIRR-seq) has become widespread, providing new insights into the immune system with potential broad clinical and diagnostic applications. However, like many high-throughput technologies, it comes with several problems, and the AIRR Community was established to understand and help solve them. We, the AIRR Community's Biological Resources Working Group, have surveyed scientists about the need for standards and controls in generating and annotating AIRR-seq data. Here, we review the current status of AIRR-seq, provide the results of our survey, and based on them, offer recommendations for developing AIRR-seq standards and controls, including future work.

Reactions to the National Academies/Royal Society Report on Heritable Human Genome Editing.

In September 2020, a detailed report on Heritable Human Genome Editing was published. The report offers a translational pathway for the limited approval of germline editing under limited circumstances and assuming various criteria have been met. In this perspective, some three dozen experts from the fields of genome editing, medicine, bioethics, law, and related fields offer their candid reactions to the National Academies/Royal Society report, highlighting areas of support, omissions, disagreements, and priorities moving forward.