The approach of the Wellcome Trust in managing intellectual property to maximise public health benefit

Introduction

The mission of the Wellcome Trust is to foster and promote research with the aim of improving human and animal health. The Trust promotes access to research results to the greatest extent possible so that they may form the basis of future discoveries and lead to public benefit. The Trust recognises that intellectual property protection (patents in particular) is a valuable tool to provide incentives for the translation of research results into products that benefit public health. To achieve its aims, the Trust believes that intellectual property issues must be approached carefully in light of individual circumstances.

The Trust's grant conditions state: "Should any Trust-funded IP arise from the Grant, then the Trust requires the Institution to consider whether the protection, management and exploitation of such Trust-funded IP is an appropriate means of achieving the public benefit." This paper aims to flesh out this requirement by illustrating what the Trust has in the past viewed as the appropriate protection, management and exploitation of IP arising from a range of funded activities1.

Over a number of years, Trust-funded research has produced a wide spectrum of potentially patentable research results that required different intellectual property management approaches2. For projects that involve production of large-scale datasets, the Trust has taken an approach that focuses on releasing data as quickly and freely as possible in order to facilitate further research. The research outcomes from these projects were generally regarded as too early on the research spectrum to have translation potential. In cases where Trust-funded researchers have approached the Trust for its consent to exploit Trust-funded IP that does have translation potential, the Trust has agreed but recommended particular conditions, such as non-exclusive licensing and reserving rights for research use, to ensure that the patent is exploited to achieve the Trust's charitable aims. The Trust does not object in principle to exclusive licensing if, in the circumstances, it is the best way of exploiting research results to achieve public benefit.

This paper presents examples from along the spectrum of research outcomes to illustrate the Trust's approach to managing intellectual property arising from biomedical research.

Some techniques that the Trust uses include:

Examples

The following examples illustrate the Trust's approach to managing intellectual property in a range of different contexts. They are ordered, generally, in progression from cases in which the Trust considered it desirable to release research results with as few restrictions on use as possible, to cases in which the grant of exclusivity was considered essential to deliver the benefits of a particular research result. In each case, the Trust has considered the particular situation in its own context to determine the most appropriate way to deliver public benefit from Trust-funded research.

Case 1: International Human Genome Project

In this case, the Trust and its partners determined that research and health objectives would be best served by releasing fundamental DNA sequence information as quickly as possible, in order to optimise coordination, independent checkin, and exploitation in both academic and commercial laboratories. Active management of IP in the data was rejected by the Trust on grounds of cost and complexity, and instead it was hoped that early release of the data would better serve the research community and still permit development of healthcare product opportunities from the basic DNA information.

The Human Genome Project was the large-scale collaboration to sequence the human genome, begun in 1990 and undertaken jointly by the Wellcome Trust Sanger Institute, US research centres funded by the National Institutes of Health (NIH) and Department of Energy, and several other institutions around the world.

The Human Genome Project had a commercial rival – Celera Genomics – which filed patents on primary genomic sequences and also wished to restrict access to its databases of sequence information to those able to pay. Other companies were patenting genes as well, for example Myriad Genetics, which filed patents on the BRCA-2 gene in 1995 the day before research teams from the Sanger Institute and the Institute of Cancer Research published results identifying mutations in the gene with an increased susceptibility to breast cancer.

The international scientific community, with particular efforts by the Wellcome Trust and the Sanger Institute, developed the Bermuda Principles in 1996 in response to the threat of fundamental genomic sequence data becoming proprietary to private companies. The Bermuda Principles advocated automatic release of sequence assemblies larger than 1KB (preferably within 24 hours), immediate publication of finished annotated sequences, and making the entire sequence freely available in the public domain for both research and development in order to maximise benefits to society. These actions were intended to allow researchers – academic and commercial – to make immediate use of the data. It was also hoped that early release of the data would lead to the prompt creation of 'prior art' that could potentially defeat patent claims based on similar DNA-sequencing efforts in the private sector.

Case 2: HapMap Project

In this case, the Trust and its partners foresaw the potential problem of other parties filing, and being awarded, patents claiming certain of the data that the Project would produce. The Project therefore used carefully established licensing terms to protect the data that it released quickly into the public domain so that individuals who filed patents would not be able to restrict other contributors' access to the data.

The HapMap Project set out to establish a map of common patterns of human genetic variation with a view to making this information quickly and freely accessible to all researchers. The Project's data release policy was intended to accelerate the work of users towards the development of products that would provide public benefit by encouraging users to develop diagnostic and therapeutic products for the treatment of human disease.

The genotype data released by the Project in its early stages was not considered patentable, as it was not sufficiently dense to allow derivation of haplotype information. The Project nevertheless identified a risk that researchers might be able to combine the Project's genotype data with their own data, to construct haplotypes, to file for patents on those derived haplotypes, and in doing so potentially restrict others from using those haplotypes and underlying data.

Before there was enough genotype information in a chromosome region to derive haplotype information, the project therefore made the initial HapMap data available only under the terms of a 'click wrap' licence. The licence did not prevent users from filing patents on SNPs or haplotypes if they found particular utility associated with them, but sought to prevent users from taking any action that would in any way restrict the access of others to the data produced by the Project.

Case 3: SNP Consortium

In this case, the Trust and its partners adopted a 'defensive patenting position' with the twin goal of releasing the data to the public as quickly as possible and at the same time establishing a prior art for use against later attempts by private companies to issue patents on the mapped SNPs.

The SNP Consortium identified and mapped 1.5 million single nucleotide polymorphisms (SNPs) from April 1999 and the end of 2001, with the objective of maximising the number of SNPs in the public domain at the earliest possible date, and for those SNPs to be free of third-party encumbrances such that they could be used by all without financial or other IP obligations. To meet these objectives the Consortium withheld public release of identified SNPs until mapping had been achieved, in order to prevent facilitating the patenting of the same SNPs by third parties. Mapped SNPs were then publicly released quarterly, approximately one quarter after they were identified.

The Consortium therefore itself applied for patents but only to establish priority dates and to secure standing as inventors (to contest other patents if necessary), but not to secure commercial patent rights. The Consortium's sequence data were published, and patent applications abandoned, after a period sufficient to prevent others from filing patent applications using Consortium data, thus preventing encumbrances on open access to those data.

Case 4: Sanger Institute material transfer agreements

The Wellcome Trust Sanger Institute has a policy of making biological resources freely available to the research community, but takes steps to protect its own use of the resources in the event that anyone should file patents on them.

The Trust and the Sanger Institute (which is wholly owned by the Trust) have developed a suite of template material transfer agreements (MTAs) for the distribution of materials created at Sanger. These MTAs contain as few restrictions as possible on the recipient of the materials and are designed to be acceptable to the majority of institutions, so that the free distribution of materials is not hampered by excessive legal negotiations. The MTAs do not contain reach-through provisions (which give the provider of materials rights to resulting inventions made by the recipient using the materials), but they do contain a non-exclusive royalty-free sub-licensable licence back to the Sanger Institute of any patents that the recipient files directly on the materials, so that the Institute can continue to distribute the materials to third parties. The new templates have greatly reduced the amount and number of MTA negotiations at the Institute and enable efficient distribution of the Institute's resources as a service to the research community.

Case 5: Diagnostics for the real world

In this case, the Trust encouraged the strategic protection of intellectual property to ensure that Trust-funded research could be fully exploited for healthcare benefit.

The Trust funded researchers at the University of Cambridge to develop a rapid point-of-care dipstick assay, appropriate for resource-poor settings, for chlamydia and other sexually transmitted diseases. The IP arising from the research was spun out into a US company, Diagnostics for the Real World. Recognising that the diagnostic assay market is a crowded IP space, the Trust was concerned that without careful IP management, there was a risk that the company could lack sufficient protection or be blocked from further exploitation of the technology. The Trust therefore made a further award to the company to establish an IP management group (including independent advisers) to advise the company on IP strategy and to carry out a freedom-to-operate analysis.

Case 6: Enzyme 11 β-HSD-1 linkage to a wide range of diseases

In the case of these patents, which are fundamental to a relatively broad field of research, the Trust recommended a non-exclusive licensing approach rather than an exclusive licensing arrangement that could potentially restrict progress in that research field.

The University of Edinburgh filed several patents relating to the enzyme 11 β-HSD-1, which is implicated in a broad spectrum of disease, from diabetes to memory loss. The inventors – leaders in their field – had received significant funding from the Trust. Under the terms of the funding agreement between the University and the Trust, the Trust managed the IP portfolio and had the first right to exploit the IP arising under the Trust funding.

To avoid the patent holding back an important area of product discovery and development, as might occur with exclusive licensing, for example to a spin-out company, the Trust therefore recommended and implemented a program of offering non-exclusive licences to parties active in the field. The licensing strategy is a balance between providing widespread access to the invention and at the same time distributing a reasonable share in the value generated by the patents to the University, the inventors and the Trust. It is anticipated that this optimises the chances of translation of the research into a valuable component of the 'knowledge economy' and a meaningful health benefit.

Case 7: ERBB2 and BRAF cancer diagnostics

In the case of this fundamental invention, the Trust intends to pursue a non-exclusive licensing arrangement to promote translation of the invention into healthcare benefit, while preserving a choice of suppliers for the healthcare user. The Trust intends this managed competition to reduce the chances that blocking or overpricing will reduce the potential health benefit of the technology.

The discovery that mutant forms of the ErbB2 and BRAF gene are implicated in various forms of cancer arose out of the Cancer Genome Project at the Sanger Institute. ErbB2 and BRAF are important targets for drugs and the mutants could have a future role in personalised medicine and clinical diagnostics. Patents were filed by the Trust on detection of the mutant ErbB2 and BRAF genes, which provide control to prevent anyone else from exploiting the inventions in a detrimental or restrictive way, and increase the attractiveness of the invention for translation by commercial or other parties into a healthcare benefit.

The envisaged translation strategy will be via non-exclusive licensing. The strategy will be to involve a combination of partners that will develop products for both the clinical and personalised medicine diagnostics sectors. The strategy is designed to avoid the potentially blocking and over-pricing risk of exclusivity while optimising the chances of a healthcare benefit emerging.

Case 8: One dose oral typhoid vaccine

In this case, the Trust has funded a company to further develop a proprietary technology for application to a disease area that was not attractive to commercial investors. The Trust has structured the IP management arrangements to encourage the company to exploit Trust-funded research itself, but retains rights to intervene if the IP is not exploited for the benefit of the developing world.

With Trust funding, the company Emergent (Europe) Limited is testing their one dose oral typhoid vaccine in healthy Vietnamese adults and children in preparation for proof-of-concept and phase III studies in South-east Asia. Emergent developed the underlying vaccine technology, which also has applicability to a number of other diseases. Emergent's commercial investors were, understandably, more focused on developing the technology for more profitable indications and were not interested in supporting early-stage clinical trials for typhoid. The Trust therefore stepped in to fund trials to address the developing world endemic market. Emergent and the Trust negotiated timescales within which the vaccine has to be launched in developing world markets. Under these terms, if launch does not take place within the agreed timescale, and the company has no concrete plans to launch within a reasonable time, the Trust can acquire the rights to manufacture and sell the vaccine in developing countries.

Case 9: Malaria drug discovery at the Novartis Institute for Tropical Diseases

In this funding agreement, the Trust included IP provisions to ensure that Trust funded research with application to diseases of the developing world is exploited to benefit those countries, and to protect ongoing basic research in this field.

The Trust, the Medicines for Malaria Venture (MMV) and the Singapore Economic Development Board agreed to fund the Novartis Institute for Tropical Diseases (NITD) to carry out a programme of drug discovery in the field of malaria, the main aims being to find a one-dose cure for Plasmodium falciparum and a curative modality for Plasmodium vivax. Novartis agreed to make contributions in kind to the cost of the programme.

NITD owns (or in the case of IP generated by collaborators, has rights to acquire rights to) all IP generated during the funded programme, but the Trust and MMV have a non-commercial research licence, to enable basic research on any findings of the programme. The Trust and MMV have step-in rights if NITD fails to file or prosecute patents so that valuable IP protection is not lost. In addition, NITD has agreed to covenants not to sue for infringement of the programme patents any not for profit institutions that may carry out non-commercial research. NITD cannot commercialise products without the consent of the Trust and MMV to the process of development. Consent is subject to a benefit-sharing arrangement. In the event that NITD puts development on hold for certain periods, or fails to make any sales into developing countries within a certain period following launch, the Trust and MMV have the option to take over the necessary IP rights, to ensure that developing countries benefit from the outcomes of the research.

November 2006

Footnotes

1The Trust also has a policy on intellectual property and patenting, with special emphasis on genomic patents. This policy was first published in 2000.

2The Trust typically has occasion to make IP management decisions at three junctures: when negotiating the terms for funding a large research programme or consortium; when funded researchers seek the Trust's consent to exploit IP (as required by the Trust's Grant Conditions); and when the Trust manages intellectual property created under the its Translation Awards scheme.