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ESHG’s Gene-Patenting Guidelines Aim to Protect Innovation and Patient Access

The European Society of Human Genetics last week issued recommendations
that would continue to allow genetic researchers to patent their innovations, including genetic tests, while at the same time ensuring that those innovations do not restrict a patient’s ability to access such tests.
The ESHG, recognizing that the genetics field introduces a new set of ethical challenges for the existing patenting system, suggested in its guidelines that geneticists and governments work together to use new mechanisms within the existing framework to reward innovation without restricting patient access.
The ESHG's recommendations, include establishing an ethics committee to assess the scope of patents and limit the granting of broad patents; more interaction among US, EU, and Japanese patent authorities to align their patent systems; prohibiting patents for disease genes; and promoting new models for licensing to promote research.
“The argument that a cDNA does not exist in nature, and thus makes its sequence patentable, is often viewed as a legal twist that does not convince most geneticists,” wrote Ségolène Aymé, Gert Matthijs, and Sirpa Soini, members of ESHG’s Public and Professional Policy Committee and the Patenting and Licensing Committee, in a paper published in the May issue of the European Journal of Human Genetics.
“The patenting of genes and genomic sequences is intrinsically different from the patenting of methods, tools and technologies, because there is no possibility to ‘invent around’ a DNA or RNA (or cDNA) sequence,” the authors state.
“The patentability of nucleic acid sequences is generally defended on the basis that they are mere chemical structures; this viewpoint neglects the fact that genetic sequences also contain genetic information, which, in addition, is shared by all humans.”
Although, in most areas, the “patenting system works satisfactorily,” the genetics field clearly introduces new ethical considerations. Thus, “it must be recognized that in some instances patents can also be problematic; this is the case in the field of genetics, and particularly in the area of genetic testing,” the authors assert in the paper.  
The authors stress that they are not proposing to overhaul the existing patenting system. Rather, they hope to encourage stakeholders to work together within the existing patenting system to find complementary mechanisms for accessing patents.
“As patents should serve their original purpose (promoting innovation through a fair reward system for the inventors), the ESHG suggests ways to improve the mechanisms that already form part of the patent system as a whole,” the authors wrote.
Matthijs told Pharmacogenomics Reporter this week that the ESHG has already had “open discussions with experts [from the European] patent office and with legal specialists” about its recommendations.
“As far as the patenting of genes is concerned, the patent office may already be adapting its policy,” Matthijs said. “The fact that there were direct interactions, is already an achievement … Of course, the patent office will never accept all recommendations that were made by ESHG.”
Describing ESHG’s recommendations covering licensing, “the next step is to try and reach the political level, so that more — and preferably European — legislation will be put in place to deal with licensing.”
Matthijs lauded the European Organization for Economic Co-operation and Development for putting out its own licensing guidelines, and suggested that other international organizations should test the feasibility of other licensing mechanisms for advancing gene patents, such as patent pools or clearing-house models.
The Recommendations
The ESHG crafted its recommendations after holding multiple workshops, starting in 2005, involving members of its Public and Professional Policy Committee and the Patenting and Licensing Committee.
Currently, under the European Patent Commission, DNA, RNA, genes, and other components of the human genome are patentable. The European Patent Office allows innovators to patent claims to DNA sequences so long as “the specification must enable the invention to be performed to the full extent of the monopoly claimed.”
While the authors acknowledge that “it is increasingly difficult to patent novel sequences, as applications are likely to require greater preparation and more biological data to support narrower claims,” they note that patent applications are likely to increase in the coming years due to growing research in the genetics field, particularly in China, India, and Korea.
While the ESHG supports the ability to patent novel tools for genetic testing, such as PCR or chip technologies, the group proposes limiting the number of gene patents by “prohibiting patenting of individual mutations in known disease genes ... on the basis of an absence of novelty.”
For instance, the ESHG has urged the EPO to consider a link between a disease and a genetic sequence to be a discovery, and therefore not patentable unless the gene-disease relationship includes “a real conceptual innovation.”

In an effort to asses the full scope of “bad” licensing practices in the field, the ESHG recommended the “genetics community and governments [to] ... analyze the availability and accessibility of genetic tests in the public sector, and identify the responsibility of the patent system if tests that exist are not available or affordable.”

According to the ESHG, many genetic claims that have been granted are too broad, and this practice has had a negative impact on the development of new innovations. In the future, European regulators should use a scientific advisory committee to assess the scope of genetic patent claims, the group suggested.
There is a need for the genetics community and governments to survey the current patent system and how it may evolve in the field of genetics in the future. “There is a need to analyze the availability and accessibility of genetic tests in the public sector, and identify the responsibility of the patent system if tests that exist are not available or affordable,” the authors wrote.
In order to assess this, ESHG suggest the establishment of a voluntary reporting system where geneticists could report any patents they perceive to be “damaging service to patients.” 
ESHG also proposes more interaction and dialogue between service providers, consumers, patent owners, and patients to find ways to preserve the patent systems without damaging the quality of care. There is a need for a balance set by legislators that provides a framework for researchers to be rewarded for their inventions without preventing access to genetic tests for patients, ESHG said.
An ethics committee should be established, according to ESHG, to consider the moral aspects of genetic patenting, particularly since attorneys, patent applicants, and patentees sometimes “push the ethical limits of patentability,” ESHG said.
ESHG also advised genetic labs to not rely on research exemptions when offering genetic tests, and suggested that new licensing models be created to encourage research in different areas and to encourage users to seek new licenses and pay royalties.
According to Matthijs, licensing mechanisms under the current patent system hinder laboratories and manufacturers of kits for genetic testing from investing in tests.
Because normal market mechanisms do not operate the same way in the genetic testing field, there should be licensing guidelines that do not give the licensor exclusive control over human genetic information, the group said. It also urged the genetic community to “respect the patenting and licensing rules,” once they are accepted, and the group said that research institutes and hospitals should know how to handle licenses and patents.
The group suggested the compulsory licenses, patent pools, and clearinghouses, may provide novel mechanisms for increasing access to genetic tests and promoting the development of new tests.
“The patenting and licensing system will be more easily accepted by the majority of geneticists and by the public, when the specific sensitivities around genetic testing, and of medicine and health care in general, are taken into account in the light of increasing (and increasingly powerful) diagnostic possibilities coming online,” ESHG concluded.
Myriad Challenges
According to the authors, only those patents that “drive innovation and promote progress” are beneficial for society. However, as more genetic tests become phenotype-based, “exploring at once many potentially involved genes,” or as genetic tests begin to combine detection of multiple gene mutations with metabolite measurements requiring combinations of patents, gene patenting may become even more complicated.
One controversy in the genetics community illustrates some of the problems with regard to innovation and patient access that might arise from an increasingly complex patenting system, as well as the importance of establishing good licensing practices. The controversy has to do with molecular diagnostics company Myriad Genetics' patenting the isolated DNA coding for a BRCA1 polypeptide and a screening method.
The company, together with the University of Utah, was the first to sequence the BRCA-1 gene, and applied for patent protection in 1994. However, in Europe many groups — including Switzerland’s Social Democratic Party, Greenpeace Germany, the French Institut Curie; the Belgian Society of Human Genetics; the Netherlands' Ministry of Health, and the Austrian Federal Ministry of Social Security — filed oppositions to Myriad's European patent (EP 705902) on the isolated BRCA-1 gene, asserting that the company failed to meet the European Patent Convention's patentability criteria requiring that an invention be novel, as well as disclose the invention sufficiently for a person skilled in the art to carry it out. 
In a 2001 resolution against Myriad, the European Parliament called on the European Patent Office to ensure the "principle of non-patentability of humans, their genes or cells in their natural environment;" and asserted that the human genome should be freely available for research purposes.
Three years later the European Parliament revoked a Myriad patent (EP 699754) that covered a diagnostic method after finding that the invention was not novel at the time of filing. Two other patents on the BRCA1 gene were amended to exclude diagnostic methods, a decision that Myriad is appealing. A patent on BRCA2 was allowed to stand in an amended form.
Ultimately, according to industry observers, Myriad's objectors took issue not so much with the validity of the patents themselves, but with the commercial application of those patents. Myriad's critics charge that its licensing policy and the high prices it demanded for its tests essentially barred other laboratories from conducting BRCA1 and BRCA2 testing.
“The influence of patents and (bad) licensing practices on the development and availability of genetic tests has been demonstrated through the BRCA case,” the authors of the ESHG recommendation paper state. “Some have argued that the problem is negligible. The ESHG acknowledges that, thus far, only anecdotal or partial data are available.”
In an effort to asses the full scope of “bad” licensing practices in the field, the ESHG has urged the “genetics community and governments [to] ... analyze the availability and accessibility of genetic tests in the public sector, and identify the responsibility of the patent system if tests that exist are not available or affordable.”
Geographic Collaboration
The ESHG acknowledged that the varying patent laws in different nations might make it even more difficult for diagnostic developers and genetic researchers to operate.
“Certain genetic inventions are patented in some countries, but not in others,” and thus “'the freedom to operate' is different in different countries,” the authors note.
Particularly, since the US Patent and Trademark Office is “more liberal” in its patenting policy than European and Japanese authorities, the ESHG said it endorses efforts of the Trilateral Organization to harmonize the varying approaches.
However, the differences in the patenting systems in different regions, might make harmonization difficult.
“The patent systems are completely separate,” Joann Boughman, American Society of Human Genetics executive vice president told Pharmacogenomics Reporter this week. “While we have not discussed (as a Board) the exact language of the ESHG policy, the basic sensibility still remains: a patent application must substantiate specific and credible utility to meet the patentability guidelines.”
Boughman cited the ASHG's response in 2000 to the US Patent and Trademark Office's “Revised Interim Guidelines for Examination of Patent Applications,” in which the group asserted its support for patenting genes with specific utility but not for patenting DNA sequences, including expressed sequence tags with no demonstrated utility.
“Use of anonymous DNA fragments or ESTs for 'real world' applications in forensics, gene mapping, or other areas almost always requires significant further research to enable a person of 'ordinary skill in the art' to use such invention,” ASHG wrote in its letter. “Moreover, since an EST represents only a part of a gene ... the patenting of multiple ESTs derived from a single gene would result in a tangled web of patent claims that would greatly complicate licensing agreements and discourage downstream research to further characterize the gene and its product.”
Similarly, the ESHG in its recommendations also asserts that the clinical utility and validity of a genetic test should be a critical determination when establishing the patentability of a genetic discovery.
“The patenting aspect is not the only issue of importance when considering the development of a new test. The assessment of its potential clinical use, the clinical validity and utility, is at least as important,” the authors wrote. The group pointed to the policies of Germany, Italy, and France, which promote “purpose-bound patent protection” to limit unnecessary broad claims, as models. 
However, currently, the clinical use, utility, and validity aspects are “not taken into account in the examination of [gene] patent applications, except through the general utility requirement,” the authors noted. “Ideally, both should go hand in hand, whereby eventually, the clinical validity and utility would influence the patenting policy.”
According to the authors, their recommendation seeks to “redefine the concept of utility in patent law, by taking account of downstream clinical experience.”
Matthijs said he hopes that the ESHG’s recommendations will at least be read by USPTO. “There is a Trilateral Organization where US, Japan, and EU patent offices meet, and I hope that that organization will at least discuss the issue,” he said.

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