New Paper

Patents and Misplaced Angst: Lessons for Translational Stem Cell Research from Genomics

Debra J.H. Mathews1Robert Cook-Deegan2 and Tania Bubela3Go To Corresponding Author 

1 Johns Hopkins Berman Institute of Bioethics, 1809 Ashland Avenue, Baltimore, MD 21205, USA
2 Institute for Genome Sciences & Policy and Sanford School of Public Policy, Duke University, Box 90141, 304 Research Drive, Durham, NC 27708-0141, USA
3 School of Public Health, Edmonton Clinic Health Academy, 11405 87 Avenue, Edmonton, AB, T6G 1C9, Canada

Corresponding author

Summary

Realizing the therapeutic potential of both stem cell and genomics research requires harnessing the respective strengths of academic, biotechnology, and pharmaceutical sectors, supported by policies and legal incentives for multisectorial collaboration. Here, we discuss issues facing these fields and lessons from the genomics sector that apply to stem cell research.
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Unique Challenges, Opportunities

Media Contact: Leah Ramsay 202.642.9640 lramsay@jhu.edu

EAST ASIA FACES UNIQUE CHALLENGES, OPPORTUNITIES FOR

STEM CELL INNOVATION

New Consensus Statement From The Hinxton Group Focuses On Japan, China

Tension is the theme running through the new consensus statement issued by the Hinxton Group, an international working group on stem cell research and regulation.  Specifically, tension between intellectual property policies and scientific norms of free exchange, but also between eastern and western cultures, national and international interests, and privatized vs. nationalized health care systems.

The consensus, titled Statement on Data and Materials Sharing and Intellectual Property in Pluripotent Stem Cell Science in Japan and China, was released on the Hinxton Group’s website Monday, November 19, 2012.

“China and Japan are among the world’s leading nations in stem cell research, but because of challenges distinct from western nations, they are dramatically underrepresented in terms of patents and licensing,” says Debra Mathews, PhD, MA, assistant director of Science Programs at the Johns Hopkins Berman Institute of Bioethics and a founding member of the Hinxton Group. Mathews was one of 22 co-signers of the consensus statement.

“We thought it was crucial, with the science advancing incredibly rapidly, and as intellectual property policies evolve in East Asia, to examine our 2010 global recommendations for proprietary issues in stem cell research in that regional context,” Mathews says.

Strengthening national stem cell innovation was the top goal articulated in Kobe, the statement says.  Whereas in the West there is a robust and mature infrastructure for encouraging and supporting the development of intellectual property rights such as patents, East Asian nations like China and Japan have comparatively less well-developed, younger systems, the group observes.  While this can make it more difficult to bring new inventions to international markets, the statement says, the opportunities created by the regional environment in Japan and China provide valuable lessons for the global development of this field.

“For example, as noted in the statement, Japan and China each have a large and highly qualified scientific workforce, paired with substantial national investment in stem cell research,” says Mathews. “This combination of factors means that both countries are well-situated to take the kinds of collective action that will be required to move the field forward efficiently and translate basic science discoveries into products and therapies.”

An area where Japan and China exercise strong state control to the possible benefit of stem cell-based invention is their national health care systems, the statement notes.  In the West, strong intellectual property rights have encouraged the “development of stand-alone blockbuster products,” the group says, whereas the national health systems in East Asia may allow patients access to more individualized, innovative treatments.  This, the group posits, could be a model for stem cell-based therapies.

“Innovation in China and Japan occurs in the context of national commitments to public health, and as a practical matter that should make access to cell-based therapies more equitable,” Mathews says.

The statement also notes the significant cultural differences that contribute to challenges — and opportunities — with intellectual property policy, practice and stem cell research in the region.  The group notes that Japan and China are “markedly less litigious” than western nations, and recognition for scientific work and publication priority are highly valued.  “Secrecy appears to be a relatively more common mode of protecting researchers’ raw [intellectual property rights], as opposed to more formalized legal systems of protection, such as patenting,” the statement says. In light of this, an appropriate incentive to sharing data and materials among scientists in the region would be the protection of their interests and rights, perhaps through a grace or priority period, the group says, during which the data is public but the original scientists have exclusive rights to publish.

The statement also discusses the challenges of sharing data and materials internationally, noting an “underlying tension between national and international interests.”  In China, for example, samples donated by citizens are considered intellectual property of the state and are governed by strict polices that create roadblocks to international sharing and access. Such policies, varying country by country, may present significant challenges to the Hinxton Group’s goal of creating an internationally coordinated stem cell bank, the statement says.

“There will always be tensions between national and international and between public and private,” as far as innovation and the protection of that innovation, the group says.  “Within the biomedical sciences, the key is to strike a balance that both promotes innovation and improves global health,” the statement concludes.

# # #

Consensus Statement: www.hinxtongroup.org/consensus_hg12_final.pdf

Japanese and Chinese translations will be posted at www.hinxtongroup.org as soon as they are available.

About the Johns Hopkins Berman Institute of Bioethics
One of the largest centers of its kind in the world, the Johns Hopkins Berman Institute of Bioethics is the home for collaborative scholarship and teaching on the ethics of clinical practice, public health and biomedical science at Johns Hopkins University. Since 1995, the Institute has worked with governmental agencies, nongovernmental organizations and private sector organizations to address and resolve ethical issues. Institute faculty members represent such disciplines as medicine, nursing, law, philosophy, public health and the social sciences. More information is available at www.bioethicsinstitute.org.

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Unsettled expectations: how recent patent decisions affect biotech

cover imageUnsettled expectations: how recent patent decisions affect biotech
Brenda M Simon Christopher T Scott
Nature Biotechnology 29, 229–230 (2011) doi:10.1038/nbt.1795
Published online: 09 March 2011

A look back shows that broad patents are a thing of the past and biotech inventors face heightened requirements for patentability.

View full text

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Hinxton Group Warns Against Stifling Effect of Widespread Patenting in Stem Cell Field

In an opinion piece published on Feb. 10 in the journal Science, a team of scholars led by a Johns Hopkins bioethicist urges the scientific community to act collectively to stem the negative effects of patenting and privatizing of stem cell lines, data and pioneering technologies. This means grappling with the ambiguity of several fundamental distinctions typically made in ethics, law, and common practice, the experts insist.

The team, led by Debra Mathews, Ph.D., M.A., of the Johns Hopkins Berman Institute of Bioethics, says failures to properly manage the widespread patenting by both private and public organizations threatens to obscure what is and what isn’t in the public domain. In addition, this disarray may well hinder progress toward breakthroughs that could lead to new treatments the public desperately wants.

“Pervasive taking of intellectual property rights has resulted in a complex and confusing patchwork of ownership and control in the field of stem cell science,” says Mathews, assistant director for science programs at the Berman Institute. “While intellectual property provides a critical incentive to take basic scientific discoveries and translate them into marketable products, transparency about such property is equally critical.”

In addition to Mathews, the commentary was co-authored by David Winickoff, an associate professor of bioethics and society at the University of California, Berkeley; Gregory Graff, an assistant professor at Colorado State University with expertise in intellectual property rights; and Krishanu Saha, a postdoctoral fellow in stem cell research at the Whitehead Institute of Biomedical Research, in Cambridge, Mass.

“Following trends seen elsewhere in the sciences,” the authors write, “stem cell researchers—and the companies and universities for which they work—are increasingly taking private ownership of early-stage technologies, cell lines, genes and associated data.”

The tracking and trading of intellectual properties is much harder than the tracking and trading of other kinds of assets, such as real estate, according to Graff. He used the analogy of the popular real estate website, the Multiple Listing Service, saying there is no equivalent public “MLS” that serves as a property records registry for stem cell researchers.

“The lack of transparency about who owns what intellectual property rights can hamper stem cell research and development,” Graff says, “and so can the resulting ambiguity of the distinction between what is private property and what is in the public domain.”

Further bogging down the field, the authors assert, is the increasing blurriness of two additional and fundamental distinctions. For one, the boundary that separates what is “information” and what is “material” gets more obscure by the day. Secondly, stem cells are not simply research material: All cell lines are derived from the tissues of human beings—people who may have an interest in the future of their genetic material and, by law, have certain personal rights that must be respected.

“Existing programs to reform science are based on a partial diagnosis of the problem,” says Winickoff. “We need a conceptual synthesis that reflects how stem cells entangle persons and things, information and materials, property and the public domain.

“A real solution to the problem,” Winickoff continues, “will have to manage all three of these complexities together, and we think we have a pathway for doing that.”

The authors echoed a recent consensus statement issued by the Hinxton Group, an international consortium of experts in stem cell science, ethics and law, which decries the increasingly secretive climate created by excessive patenting and proprietary claims within the stem cell community.

AAAS panel discussion“There are very real concerns in industry about freedom to operate and concerns about lawsuits down the line, once they’ve invested a huge amount of money—and then, a patent pops up that they didn’t know about,” Mathews, a member of the Hinxton Group, said at a Jan. 24 panel discussion that coincided with the release of the consensus statement.

Both the statement and today’s  article in Science call for collaborative information and materials hubs that would broaden access and help clarify what types of information are rightly proprietary and what types are not. One such hub, the authors suggest, might take the form of a centralized portal for access to existing databases, such as the UK Stem Cell Bank and the Human Embryonic Stem Cell Registry .

The authors also acknowledge that major challenges to the development of that and similar resources include securing funding, designing and programming talent, and deciding who would provide ongoing, administrative oversight.

Media contact: Michael Pena

mpena@jhu.edu; 410-614-5381


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Consensus Statement

Statement on Policies and Practices Governing Data and Materials Sharing and Intellectual Property in Stem Cell Science [pdf]

  • Recommendation 1a
    Establish a central hub for accessing global stem cell registry information
  • Recommendation 1b
    Establish a central hub for accessing information about stem cell patents
  • Recommendation 2
    Encourage, support and coordinate international human stem cell banks and human tissue and cell repositories
  • Recommendation 3
    Develop and institute incentives for data and materials sharing through publication, participation in information hubs, and other mechanisms
  • Recommendation 4
    Explore options for formal collaborative networks, patent brokering, and formation of patent pools when those mechanisms for collective management of intellectual property can move the field forward
  • Recommendation 5
    Adopt licensing practices and patent policies that promote fair, reasonable, and nondiscriminatory (equitable) access to knowledge and health care applications
  • Steering Committee
  • Executive Committee
  • Other Members
  • Funders

PREAMBLE

Tension is increasing between fairly new and pervasive policies and practices governing data and materials sharing and intellectual property in science (‘proprietary structures’), and norms of openness and free exchange. While intellectual property rights (IPR) can bring private investment into areas underfunded by governments and help bridge gaps between scientific invention or discovery and useful technologies, some new and emerging policies and practices risk slowing innovation in research and development (R&D) and skewing attention toward large markets, to the disadvantage of small markets, such as those for rare diseases and in some emerging economies. This is of concern, as one central goal of the life sciences is to improve global health: our shared humanity and the potential for biological knowledge to benefit all people create this obligation. Further, the self-regulatory structures within scientific communities, as much as the legal institutions we consciously erect for science, should be responsive to this goal.

While the proprietary dilemmas currently faced in stem cell science confound many if not all areas of cutting edge life science, they are especially pronounced in the field of stem cell research. First, the tree-like shape of cellular differentiation makes the field especially prone to IPR holdings that can function as tollbooths to broad areas of work, creating a drag on investment and slowing down basic research. Second, the consequences of such slowing are especially severe in the stem cell field, where novel cell lines, reagents and related technologies function as platforms for broad areas of follow-on work.  Third, the competition to stake out aggressive patent positions is accentuated in the current context of competitive national innovation policies featuring stem cell science.

It should be noted that our research and deliberations focused primarily on human pluripotent stem cells (embryonic stem cells—ESCs, and induced pluripotent stem cells—iPSCs), and their derivatives, rather than tissue specific stem cells, in part because the ability to derive human pluripotent stem cells is relatively new and because of the considerable excitement these cells have generated (political as well as scientific), but also because their origins and very nature create special problems relating to IPR. Indeed, the pluripotency of ESCs and iPSCs is a major issue in terms of utility and overlapping patent claims. However, it is quite likely that many of our deliberations and recommendations could equally apply to tissue specific stem cells, whether these are fetal, umbilical cord blood, or adult in origin. We encourage those working on these other stem cell types to consider adopting similar measures to those proposed here and to contribute to common resources for data and materials.

Human pluripotent stem cell science is a young field, but one that has already progressed from initial invention to enrolling the first subject in a clinical trial. This rapid progress has occurred in the public eye, against a background of significant moral disagreement within and across nations, and within a complex regulatory environment hosting a patchwork of divergent and often conflicting responses. Furthermore, with its great potential to advance both basic and translational science, stem cell research has become a focus of national economic, innovation and competitiveness strategies. And finally, though many fields of science have reached a similar point in their development, now is the time in stem cell science for the sorts of collective reflection and action proposed herein.

This statement has benefited from the input of an international group of stem cell scientists, scholars of IPR and innovation, ethicists, lawyers, physicians, and representatives from funding bodies, governmental bodies, industry, and scientific journals. In this statement, we make several recommendations to address the challenges raised by proprietary practices and policies in stem cell research in a way that promotesboth scientific innovation and the public good. Admittedly, we do not address all issues faced by stakeholders in this arena; we have tried to target challenges faced by multiple stakeholders and for which we could develop concrete and actionable recommendations. We also acknowledge that some of the most important ways to align stem cell research with the goal of global justice pertain less to IPR, and more to the kinds of research questions that are asked, and the sorts of projects that find funding.

While we do not, by our constitution, represent the views and interests of all the varied stakeholders in the stem cell science enterprise, we do hope this statement will nonetheless help to articulate the kinds of global obligations we share in the study of biology writ large, and how those obligations may be honored in the field of stem cell science. We also hope that these recommendations will help stimulate a broader dialogue among communities, scientists, patients, ethicists, regulators, and others about how proprietary practices and policies in stem cell research can best serve the global public interest.

Recommendation 1a. Establish a central hub for accessing global stem cell registry information

Statement of the Problem

Data sharing is a critical factor in the progression of stem cell science; though currently, sharing is hampered by the behavior of individual scientists and laboratories, the speed with which the field is moving, and by fragmentation of data across local, regional and national registries and banks, and the related barriers to knowledge of and access to this disparate set of resources. In part due to the speed with which the field is moving, many cell lines are being derived and characterized, though not all lines are being published in the literature, even in the academic sector. Furthermore, useful cell lines created from human materials (especially those created with public funds) and their associated data should be distributed and used widely, constrained only by the wishes of the materials‘ donors.

Recommendation

A publicly available central hub or information portal for accessing global stem cell registry information should be established and maintained as a resource for and service to the community, easing access to information and reducing barriers to sharing. The Global Hub for Stem Cell Registry Information should enhance and create linkages between and build upon existing efforts (e.g., the NIH Human Embryonic Stem Cell Registry, the International Stem Cell Registry at the University of Massachusetts, the European Human Embryonic Stem Cell Registry).

A good model for such a linked resource is the network of three publicly funded databases used for DNA sequence data, protein data, and other biological information: GenBank at the National Center for Biotechnology Information (NCBI; Bethesda, Maryland, USA); EMBL-Bank at the European Bioinformatics Institute (EBI; Hinxton, UK); and the Center for Information Biology and DNA Data Bank of Japan (Mishima, Japan). Each of the three groups collects a portion of the total data, and all new and updated database entries are exchanged between the groups on a daily basis. Thus the funding, physical security, transparent operation and collective ownership of the database as a whole is assured more securely than if it were located in a single place. Data in the public databases are free to anyone to read, to download and analyze without restriction, including for commercial use, and in the context of clear rules for appropriate access and attribution.

Databases, such as these and others [e.g., the Kyoto Encyclopedia of Genes and Genomes (KEGG)] have proved successful for a number of reasons. First, there was collaboration among stakeholders (journals, funding agencies, governments) and the development of incentives for participation (e.g., priority rules and the need for a common database against which to compare newly discovered sequences). Database operators negotiated with major scientific journals to establish database accessions as a requirement for publication. This became standard practice in the field as other journals followed suit, and assured open access to research results. In the same way, provision of stem cell information to the Global Hub or one of its constituent registries could be made a condition for grants and publications; alternatively, it could be left voluntary with incentives to contribute. The goal is a successful data resource, as measured by how comprehensive, complete, and accessible it is.

The ‘linking’ function of the Global Hub will require coordination and cooperation across many organizations, along with a robust programming effort to allow the hub to usefully draw from diverse databases and resources. Agreements to store data in a standard format across databases will be crucial to success. At minimum, the Global Hub should include information on cell lines (including those with specific mutations, those created for screening/discovery purposes, those with potential medical utility, etc.), and any associated attributes (such as characterization data and provenance information) that can be gleaned from available sources; research tools (reagents, technologies and methods); and, publication information (via links to PubMed and the relevant journals). For the sorts of data that should be available for cell lines, proposed and evolving standards should be consulted (e.g., the International Stem Cell Banking Initiative’s Consensus Guidance for Banking and Supply of Human Embryonic Stem Cell Lines for Research Purposes), but should include accession numbers for related materials, as well as such information as donor ethnicity, HLA phenotype, sex, available clinical history and informed consent details, including any restrictions put on the use of the cells.Agreement on a minimum data set (for both characterization and provenance) for cell lines included in the associated databases will maximize the utility of the resource.

Recommendation 1b. Establish a central hub for accessing information about stem cell patents

Statement of the Problem

Many research institutions, private entities, and individuals have obtained patents relevant to stem cell research and its application. These patents have been studied by individual groups of scholars. Some of the main conclusions from that body of scholarship are that (1) the public databases of patents are often difficult to search, and can be out of date, and incomplete; (2) despite generally similar legal criteria, the outcomes of patent examination in different patent jurisdictions are quite different; (3) IPR are copious and atomized into a profusion of patents with overlapping claims; and (4) no one is curating the global body of patent data. This has created a situation in which even a diligent stem cell researcher or entity that wishes to respect IPR will face considerable uncertainty and enormous costs if they try to survey the IPR landscape. Everyone suffers when there is no map for a new research area, and individual explorers are in no position to do the mapping and have no incentive to satisfy the needs of other stakeholders.

Recommendation

We propose the creation of an Information Resource for Stem Cell Intellectual Property Rights (IPR Resource) that would function as a field-specific hub to link and build on existing resources, such as the patent landscaping efforts of the Japan Patent Office and the UK Intellectual Property Office, and academic efforts, including work of the Stanford Program on Stem Cells in Society. The IPR Resource would link all relevant facets of stem cell IPR and represent a searchable database of primary patent data, i.e., patents and patent applications (e.g., drawing on the newly online US Patent Application Information Retrieval system, private patent compiling services, etc.), and be linked tosecondary resources, such as related academic publications (via PubMed, and including both scientific manuscripts and those on stem cell IPR), cell line information, etc. [The Public-Sector Intellectual Property Resource for Agriculture (PIPRA) and the Database of Genotypes and Phenotypes (dbGaP) represent partial models for this.]

As with the Global Hub, the ‘linking’ function of the IPR Resource will require coordination and cooperation across many organizations, along with a robust programming effort to allow the hub to usefully draw from diverse databases and resources. The ‘building’ function of the IPR Resource will require staff, and the development and maintenance of the set of documents that are not being captured by existing resources that could feed into a hub (e.g., information from patent offices not covered by searchable patent databases). Staff will also be needed to search for and capture available licensing and assignment information (i.e., scanning the trade press, Securities and Exchange Commission filings, company annual reports, etc.), and scholarly literature that presents first level analysis of the evolving landscape of stem cell patents (e.g., landscaping). There is, of course, a language problem that will need to be addressed, as patents, government documents, and academic literature are not written in a single, common language globally. There may also be a role in the IPR Resource for a wiki-type component, wherein scholars and other experts in the field develop patent digests for selected technologies, or otherwise help curate the resource.

A resource such as the one proposed here will require both champions and funding. We envision an international consortium of public and private funding partners, with interests in science, innovation and equitable access to information.

Recommendation 2. Encourage, support and coordinate international human stem cell banks and human tissue and cell repositories

Statement of the Problem

Many individual labs in academia do not have the capacity to share cell lines broadly; however, norms of open science presume broad circulation of data and materials, in part to reproduce results as a basic tenet of science. In addition, consent documents signed by tissue donors frequently refer to benefits for particular communities, and usually for general public or societal benefit. Currently, many human pluripotent stem cell lines are being derived in laboratories around the world, though norms around storing and sharing these lines are unsettled. Among all the individual parties using existing banks, there are duplicated legal negotiations, especially around material transfer agreements (MTAs), and duplicated investigations of provenance that delay the sharing of materials. Differing operating procedures and end uses across research and clinical domains also create challenges. Furthermore, the scientific enterprise is developing in the direction of desiring to acquire increasing levels of medical information associated with the tissues used to derive cell lines, and we may need new, internationally coordinated mechanisms to deal with emerging issues related to informed consent and privacy.

Recommendation

a. Current human pluripotent stem cell banking efforts (e.g., UK Stem Cell Bank) already address some of the challenges of materials sharing and should be encouraged, funded, and coordinated internationally.

b. Existing cell banks and repositories should coordinate with regard to standards, and network across national boundaries and disease communities; this could have synergies in enhancing access for the general research and development community. While not necessarily global in scope, a well-networked international set of cell banks and repositories could quickly and efficiently distribute existing and newly generated human stem cell lines of common interest. In addition to stem cell banks, banks of human tissue or differentiated cells (e.g., skin fibroblast cells) could also provide cells to the stem cell community that could be reprogrammed and circulated in a similar fashion to provide a comparable level of access. Cell and tissue banks, over time, develop expertise that can be used to develop standards, such as in cell culture and storage methods, and coordinate practices of data, cell and tissue distribution (see the International Stem Cell Banking Initiative’s Consensus Guidance for Banking and Supply of Human Embryonic Stem Cell Lines for Research Purposes).

c. Importantly, and in addition to circulating materials within the research community, many banking efforts also manage provenance information related to the human materials they bank. This practice should be adopted and coordinated across cell banks and repositories, as provenance investigations and findings facilitate the critical function of ensuring that consent for research uses at the procurement stage is honored as R&D are pursued with the resulting stem cell lines.

d. Given the costs of maintaining such banks, these efforts could encompass, initially, a small set of well-characterized human iPSC lines. The selection of particular cell lines should be justified and transparent. For example, a criterion for inclusion of cell lines could seek a balance between how popular these lines are in the academic community versus how applicable they are for particular therapeutic efforts, and deliberation on this balance should be publically available. Another relevant criterion may be the level of constraint on the use of a cell line based on the consent obtained at the time of materials procurement.

Recommendation 3. Develop and institute incentives for data and materials sharing through publication, participation in information hubs, and other mechanisms

Statement of the Problem

In a rapidly expanding field with numerous publications reporting on research involving stem cells, it can be difficult to access certain types of data (e.g., cell characterization data), and such data are often not easily comparable across publications. Moreover, there is concern about the efficient sharing of materials, especially in an international and often competitive environment. Currently, there are disincentives to early publication and distribution, especially in industry: competition is restricting data and materials sharing both within and across academia and industry; there is a lack of vehicles for publishing certain types of data (especially negative data); and, there is a reluctance to distribute materials after publication. Recommendations 1 and 2 are concerned with the establishment and operation of central information hubs and cell banks to help ameliorate these problems. However, the utility of these hubs and banks is dependent on the participation of scientists, research institutions, funders and governments.

Recommendation

a. Funders, research institutions and journals should encourage and support the establishment of relevant databases and/or “hubs” where these do not already exist, and where and when they do, insist on the deposition of data, with release on (or in a specified time after) publication. There is a comparable model successfully used by the top 20 clinical journals (e.g., NEJMLancetBlood), begun by the US National Institutes of Health in 2000: ClinicalTrials.gov. This site features 90,000 clinical trial records. Trial aims and design must be registered before any results will be published. Other relevant examples include the Minimum Information About a Microarray Experiment (MIAME) standards, which describe the data deemed necessary to evaluate and reproduce a published experiment, and to which over 50 journals hold microarray-based papers as a condition of publication; the Bermuda Principles, which reinforced the existing genome databases; and databases and biomaterial repositories for model organisms—e.g., the mouse resources at the Jackson Laboratory, the KOMP Repository of the Knockout Mouse Project, FlyBase (for Drosophila), WormBase (forCaenorhabditis elegans). Many scientists are already used to dealing with these and similar repositories, and recognize the benefits of submitting data and materials, the advantages they give in efficiency and cost of distribution, and the added value these repositories provide to the relevant communities.

b. Funding bodies and journals should insist that sufficient information is provided on methods in (or associated with) a publication, to allow other researchers to evaluate and replicate published experiments. In the event that it is discovered post-publication that insufficient methodology accompanied a manuscript, there should be mechanisms to add this information in a way that it is linked to the paper, via a mechanism similar to corrigenda and errata, perhaps as Amendments.

c. Regulatory bodies, research institutions, funding bodies, companies, and journals should develop a consistent policy for sharing data and materials post publication. Support for these activities should be itemized in research grants, and mechanisms should be implemented to monitor compliance with the policy.

d. At the time of submission for publication, funders and journals should inquire and researchers should share whether any useful negative data were generated in the course of a project. If so, this information should also be made available in publications, as supplementary data or as an accession number to a research information database or hub. Mechanisms may be required to ensure that negative data have been obtained in a rigorous manner, which may impose an unfair burden on journals and reviewers. It is therefore recognised that additional incentive and support mechanisms may need to be developed.

e. Scientists and clinicians should advise journals and funders on appropriate standards for data completeness and norms of behaviour that should be incorporated into guidelines or rules.

Recommendation 4. Explore options for formal collaborative networks, patent brokering, and formation of patent pools when those mechanisms for collective management of intellectual property can move the field forward

Statement of the problem

Copious IP, including patents, has accumulated. Collective action could be taken to reduce transaction costs and bureaucratic friction that can intrude on market mechanisms to advance stem cell R&D and its early clinical applications. The profusion of patents signals that individual research institutions are hedging their bets, seeking patent rights as a matter of course, in the unlikely event that one of these patents will result in a huge financial payoff, but thereby creating a culture of pervasive patent infringement married to a potential option for prosecuting selected infringement later. The result is a broad shadow of uncertainty about freedom to do research and pursue applications. Another result is likely to be under-investment in new firms, high barriers to entry for new innovators, and slower progress for the field than if individual research institutions were more constrained and targeted in their seeking of patent rights. No one can move ahead without fear of later encountering lawsuits by patent-owners, and yet many of the key patents are held by research institutions with public missions.

Collective resources, such as cell banks and registries; central hubs, such as those proposed elsewhere in this document; and consistent policies among research institutions and funders can reduce some friction. It seems likely, however, that some form of collective management of accumulated IPR may also be needed. Of note, the recent US National Research Council report on “Managing University Intellectual Property in the Public Interest” makes clear that the missions of creating knowledge and disseminating knowledge need to guide the patenting and licensing policies of universities and nonprofit research institutions.

Recommendation

Intellectual property relevant to stem cell research has several features in common with other technologies, but some features that are distinctive. Many patents have been granted in different countries and multinational patent jurisdictions (such as the European Patent Office). The accumulation of IPR is common for an emerging technology, and since 1998, this has been occurring in human pluripotent stem cell research and its applications.

The main challenge in forming collective resources is usually the recognition by a critical mass of the stakeholders that a particular problem worth solving or a particular opportunity worth exploiting exists. The frequency of laboratories and companies encountering delays and blockages may be rising fast enough, in at least some domains of stem cell research, to mobilize a consensus that the emerging IPR problems need to be addressed. The IPR surrounding iPSCs in particular are accumulating rapidly, the patent holders are diverse and numerous, and new patents are emerging on a complex patent landscape. The time may be ripe for collective action to ensure that R&D proceeds apace, and with less congestion or friction than is likely to be possible without such coordinated action.

There are several options for disposing of the accumulated IPR in a way that benefits all parties. The Information Resource for Stem Cell Intellectual Property should explore options for collective management of IPR, and identify areas in which patent pools, formally constructed semi-commons, etc., may be warranted.

Options

Patent Pools. Formal patent pools are one possible solution to reducing transaction costs around particular applications or standards (this may include iPSCs). Patent pools require a collection of issued patents that patent holders agree to “pool,” meaning that they have a formal contractual agreement to not enforce the patents against one another or against others licensed by the pool. A pool requires valid patents, a gatekeeping function to determine what belongs or does not belong in the pool, a way to value and return revenues for patents in the pool, and sufficient common interests among the patent-holders to be sustained.

Three factors may make it difficult for a formal patent pool to emerge in stem cell research: (1) the claims in patents need to be valid, yet it appears that overlapping claims exist and that many broad and sweeping claims have been granted, as such, invalid claims would need to be weeded out by re-examination or legal analysis, and only patents with valid claims that can withstand legal challenge should enter the pool; (2) the interests of universities, nonprofit research institutions, small firms, and large firms using the patented inventions may not be in sufficient alignment to support a pool, and yet all those entities hold patents; (3) the valuation of the patents in the pool can be vexing, as patents may have very different value but there may be no consensus about perceived relative value, and disagreement over the formula to allocate rewards for use. Patent pools could nonetheless emerge but will likely include only a small fraction of the patent rights that have been granted to date and in the foreseeable future.

Use-now pay-later semicommons. Another model for collective management of IPR involves a set of rules designed and enforced by stakeholders, through a network of agreements. Some agreements may be informal, but a subset of rules and practices needs to be written and formal. The formation of norms and practices around IPR is easier when there is a small number of research funders, but in stem cell research, the emergence of the field from small companies, individual universities and funding by state governments within the US, and many regional and national governments internationally, but without a dominant funding organization, has led to an unusually intense problem of research coordination, coupled to a profusion of IPR held by disparate actors with divergent interests. The development of a semicommons may be a way to address this.

Patent brokers. Short of a formal patent pool, if patent-holders have generally similar licensing strategies, collections of patents managed by a neutral arbiter could emerge. A “patent supermarket” does not require a strong gatekeeper to vet the patents entering a formal pool, but only a broker to collect patents available to potential licensees to be made available on standard terms. A royalty “clearinghouse” can consolidate and simplify the transactions of incremental royalty payments for such standard term licenses.

Collaborative networks. One promising strategy is to reduce transaction costs by eliminating patents that are never enforced, licensing existing patents on nonexclusive terms except when exclusivity is needed to induce investment in product development, and generally clearing out the accumulated underbrush of IPR detritus. These actions require changes in policy among individual stakeholders in the field, and are likely to emerge only if there are explicit norms articulated by those engaged in stem cell research.

Recommendation 5. Adopt licensing practices and patent policies that promote fair, reasonable, and nondiscriminatory (equitable) access to knowledge and health care applications

Statement of the Problem

We believe that licensing practices in the biological and biomedical sciences should reflect the goal of global justice, borne out of a human dignity common to all and a universal commitment to reduce suffering. Intellectual property is not simply a private matter: in addition to its obvious benefits and consequences for owners and users (licensed or not), it provides frameworks variably incentivizing invention and writings in accordance with societal aims, backed by the power of the state. Like real property, its state-backed power to exclude must necessarily be accompanied by awareness of its social context and utility, and reasonable limits on its use in the form of obligations towards others. With research using human materials, the case for requiring broad social benefit arguably becomes even stronger. Finally, the altruism of donors and the commitments made to ethics review bodies, funders and others, require that institutional licenses match any intention for social good promised by researchers.

Recommendation

The ethical importance of promoting access to knowledge and medicines through good licensing practices is self-evident. Accordingly, statements in this vein made by a number of professional societies must be not merely affirmed but also implemented. These statements include, but are not limited to, “In the Public Interest: Nine Points to Consider,” endorsed by the Association of University Technology Managers; the Intellectual Property provisions of the International Society for Stem Cell Research (ISSCR) Guidelines for the Conduct of Human Embryonic Stem Cell Research; and the Social Justice provisions of the ISSCR Guidelines for the Clinical Translation of Stem Cells.

a. In particular, any licensing on government-funded stem cell inventions must:

  • Reserve research rights for non-profit institutions;
  • Promote R&D on and access to technologies that can help meet critical health needs in both developing and developed nations. This can be facilitated through the use of, wherever possible, negotiated global access terms and jurisdictional and field-of-use limitations;
  • Use non-exclusive licensing of platform technologies and technologies of broad ancillary utility that are instrumental to the development of the field; and,
  • Ensure that data and materials are available to government and academic researchers with a minimum of delay.

Licensing of privately funded stem cell inventions should also consider the above recommendations.

b. Technology transfer offices in government-funded research institutions should make public their stem cell IPR, including their geographic scope and licensing history (including where rights have been reserved or non-assert clauses have been used), in order to promote transparency and greater use of stem cell technologies. This could be done easily and inexpensively with the IPR Resource proposed elsewhere in these recommendations.

c. Patent offices and key policymakers should reassess whether the current standards for granting stem cell patents are appropriate, given both the power of broad platform patents to block R&D, and the proliferation of patents that can create uncertainty and fragmentation in the patent landscape.

Steering Committee:

Sarah Chan, BSc(Hons), LLB, MA (Health Care Ethics and Law)
Deputy Director & Research Fellow in Bioethics and Law
Institute for Science, Ethics and Innovation
School of Law, University of Manchester
mail: sarah.chan@manchester.ac.uk

Peter J Donovan, PhD
Professor, Departments of Biological Chemistry and Developmental & Cell Biology
Co-Director, Sue & Bill Gross Stem Cell Center
University of California – Irvine
Email: pdonovan@uci.edu

Ruth Faden, PhD, MPH
Philip Franklin Wagley Professor of Biomedical Ethics
Executive Director, Johns Hopkins Berman Institute of Bioethics
Professor, Department of Health Policy & Management , School of Public Health
Professor, Department of Medicine
The Johns Hopkins University
Email: rfaden@jhsph.edu

John Harris, FMedSci, BA, DPhil
Lord Alliance Professor of Bioethics
Director, Institute for Science,
Ethics and Innovation
School of Law
University of Manchester
Email: john.harris@manchester.ac.uk

Robin Lovell-Badge, PhD, FMedSci, FRS
Head, Division of Developmental Genetics, MRC National Institute for Medical Research
Division of Developmental Genetics
MRC National Institute for Medical Research
Email: rlovell@nimr.mrc.ac.uk

Debra JH Mathews, PhD, MA
Assistant Director for Science Programs, Johns Hopkins Berman Institute of Bioethics
Assistant Professor, Department of Pediatrics
The Johns Hopkins University
Email: dmathews@jhmi.edu

Alan Regenberg, MBe
Bioethics Research Manager, Johns Hopkins Berman Institute of Bioethics
The Johns Hopkins University
Email: aregenbe@jhsph.edu

Julian Savulescu, BMedSci, MB, BS, MA, PhD
Uehiro Chair in Practical Ethics
Director, Oxford Uehiro Centre for Practical Ethics
University of Oxford
Email: julian.savulescu@philosophy.ox.ac.uk

David Winickoff, JD
Co-Director, Science, Technology, and Society Center, University of California Berkeley
Associate Professor of Bioethics and Society
University of California – Berkeley
Email: winickoff@berkeley.edu


Executive Committee:

Robert Cook-Deegan, MD
Director, IGSP Center for Genome Ethics, Law & Policy
Duke University

Gregory Graff, PhD
Assistant Professor, Department of Agricultural and Resource Economics
Colorado State University

Aurora Plomer, BA, MA, LLB, PhD
Chair in Law and Bioethics, Director of SIBLE, School of Law, University of Sheffield
Director, Sheffield Institute of Biotechnology Law and Ethics
University of Sheffield

Kris Saha, PhD
Postdoctoral Fellow, Whitehead Institute for Biomedical Research, MIT
Science Technology and Society Fellow, Kennedy School of Government
Harvard University

Christopher Scott
Director, Program on Stem Cells in Society, Center for Biomedical Ethics, Stanford University
President/CEO, The Stem Cell Advisors

John Sulston, PhD
Chair, Institute of Science, Ethics, and Innovation
University of Manchester School of Law
University of Manchester

Patrick Taylor, JD
Fellow, Petrie-Flom Center for Health Law Policy, Biotechnology and Bioethics, Harvard Law School
Assistant Clinical Professor, Harvard Medical School
Staff Scientist, Children’s Hospital, Boston, MA


Additional Hinxton Group Members:

Elona Baum, JD (Observer*)
General Counsel
California Institute of Regenerative Medicine

Laura Biron, PhD
Greenwall Fellow in Bioethics and Health Policy, Johns Hopkins Berman Institute of Bioethics
The Johns Hopkins University

Tania Bubela, PhD
Assistant Professor, School of Public Health
University of Alberta, Canada

Francesca Cesari, PhD (Observer*)
Senior Editor
Nature

Haidan Chen, PhD
Post Doctoral Research Fellow, Center for STS
Zhejiang University, China

Jorge Contreras, JD
Director, Intellectual Property Program, School of Law
Washington University in St. Louis

Ishan Dasgupta
Research Program Coordinator, Johns Hopkins Berman Institute of Bioethics
The Johns Hopkins University

Matthew DeCamp, MD, PhD
Greenwall Fellow in Bioethics and Health Policy, Johns Hopkins Berman Institute of Bioethics
Fellow in General Internal Medicine
The Johns Hopkins University

Richard Gold, SJD
Associate Professor, McGill University Faculty of Law
President, Innovation Partnership

Søren Holm, BA, MA, MD, PhD, DrMedSci
Chair, Center for Social Ethics and Policy, University of Manchester
Professor of Medical Ethics, University of Oslo

Jim Houlihan, PhD (Observer*)
Head of Innovation Policy
UK Intellectual Property Office

Ryuichi Ida, LLB, LLM
Professor of International Law, Kyoto University Graduate School of Law
Member, Expert Panel on Bioethics, Council for Science and Technology Policy, Japan
Member, Bioethics & Biosafety Committee, Ministry of Education, Culture, Sport, Science & Technology, Japan

Kazuto Kato, PhD
Associate Professor of Science Communication and Bioethics, Institute of Research in Humanities, Graduate School of Biostudies
Kyoto University

Annabelle Lever, PhD
Wellcome Interdisciplinary Research Fellow, Institute of Science, Ethics, and Innovation
University of Manchester

Jacob Leveridge (Observer*)
Biomedical Ethics & Medical Humanities Adviser
Wellcome Trust

Reinhard Merkel, Prof, Dr
Institut für Kriminalwissenschaften
Universität Hamburg

Dianne Nicol, PhD, LLM
Professor
University of Tasmania, Australia

Amanda Odell-West, PhD
Lecturer in Law, School of Law
University of Manchester

Beverly A Purnell, PhD
Senior Editor
Science Magazine

Mahendra Rao, MD, PhD
Vice President, Stem Cells at Invitrogen
Adjunct Professor, Buck Institute of Age Research
Vice President, Medicine at Life Technologies

Brock ReeveMPhil, MBA
Executive Director, Harvard Stem Cell Institute
Harvard University

Mark Rohrbaugh, PhD, JD (Observer*)
Director, Office of Technology Transfer
National Institutes of Health

Mark Sheehan, PhD, MA
BRC Ethics Fellow, The Ethox Centre
James Martin Research Fellow in the Program on the Ethics of the New Biosciences
Oxford University

Glyn Stacey, PhD
Head of Division of Cell Biology and Imaging, National Institute for Biological Standards and Control
Director, The UK Stem Cell Bank

Jeremy Sugarman, MD, MPH, MA
Harvey M Meyerhoff Professor of Bioethics and Medicine
Deputy Director for Medicine, Johns Hopkins Berman Institute of Bioethics
The Johns Hopkins University

Dieter Treichel, PhD
Patent and Start-up Manager
Max Planck Innovation

Fanyi Zeng, MD, PhD
Professor, Associate Director, Shanghai Institute of Medical Genetics, Shanghai Stem Cell Institute
Shanghai Jiao Tong University, China

*Observers participated in the Hinxton Group meeting as interested parties, but are unable to formally endorse the consensus statement due to their professional positions

Funders

We would like to gratefully acknowledge the generous support of the institutions funding this work:


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Thank You!

I’d like to offer a sincere thank you to all of our Hinxton Group members for generously sharing your time and talents!  We will be in contact soon with the recommendations document, and look forward to continuing collaborations.

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Additional Resources

Courtesy of Jim Houlihan, here are links to useful resources that were mentioned during our meeting.

Patent landscaping in stem cells which sits on the UK stem cell network site – clearly this can be configured on global data sets.

http://www.uknscn.org/downloads/patent_analysis_0811.pdf

Overview of the UK National Stem Cell Network Patent Watch Landscape (pdf)

Manchester’s IP Pool-which is now called the “IP Net”

http://www.theintellectualproperty.net/ -See “browse offers” in particular.

Also I mentioned to some people the “Lambert tool-kit for collaborative research” – this includes a series of contracts for different scenarios and more fundamentally an iterative educational guide.

http://www.ipo.gov.uk/whyuse/research/lambert.htm

Lastly, the European Innovative Medicines Initiative, the world’s largest PPP in healthcare 2B Euro – there’s a section on the IP policy. http://www.imi.europa.eu/content/documents#ip_policy.

 

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