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In Contentious Meeting, SACGHS Tackles Gene-Association Patentability, Impact of Exclusive Licenses

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By Turna Ray

A high-profile government advisory committee was minutes away last week from formally recommending that HHS Secretary Kathleen Sebelius support statutory changes limiting the practice of patenting claims on genes — but at the very end of a one-and-a-half-day meeting on gene patenting, the HHS Secretary's Advisory Committee on Genetics, Health, and Society decided to hold off on voting on the group's recommendations until the opinions of dissenting members were incorporated into the full report.

The SACGHS task force on gene patents and licensing practices last week recommended the HHS Secretary support and work with the Secretary of Commerce to promote statutory changes that would exempt from infringement liability anyone developing or selling a test based on patent claims on genes for patient care or for research.

Recognizing that these recommendations, which would require statutory changes and congressional action, may take time to be enacted, the task force proposed intermediary proposals urging industry and academia to practice ethical licensing practices; discouraging and restricting single-laboratory exclusive licenses; creating an advisory body to assess the impact of gene patenting and licensing practices; and clarifying whether the Bayh-Dole Act gives agencies the power to influence how patent holders license their inventions.

Additionally, the task force recommended the creation of an expert panel to advise the US Patent and Trademark Office on the scientific and technological advancements related to gene patents to help develop guidelines on non-obviousness and subject-matter eligibility once pending patent cases are decided.

If the committee's main recommendations "were immediately actionable, then we wouldn't need these [intermediary] recommendations, but we all know that's not going to happen," said Steven Teutsch, SACGHS chair and chief scientific officer of the Los Angeles County Department of Health.

The recommendations were met with resistance from several committee members who criticized the recommendations as inactionable for the HHS Secretary, charged that the task force had paltry evidence to support its recommendations, and warned that the recommendations were so broad they would be disruptive to the entire US patent system.

Mara Aspinall, former Genzyme president and SACGHS member, was the main voice of opposition in the task force. Aspinall and two other committee members — Sheila Walcoff, a partner at the law firm McDermott, Will & Emery, and Paul Billings of GeneSage — voted against or absented from voting on most of the committee's recommendations.

Brian Stanton of REDANDA group, an ad hoc expert on the task force, was absent from the meeting, but issued a statement calling the proposal "ill-conceived and fatally flawed to such an extent that it serves no purpose."

Additionally, during the public comments portion of the meeting, a spokesperson from the Biotechnology Industry Organization and the Wisconsin Alumni Research Foundation spoke out against the committee's recommendations as having a negative impact on patient access and innovation.

The task force on gene patents and licensing practices was led by James Evans, director of clinical cancer genetics at the University of North Carolina – Chapel Hill, who urged against delaying a vote based on the opposition of a minority.

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"We went over this for eight hours yesterday. We voted on every recommendation. We made a few changes," Evans said. "I would move that we approve or not approve this report. And as we have done with many of the reports, there can be word-smithing to try to change some of the text, but the recommendations would not be [changed in] substantial ways."

Responding to concern among dissenting members that the report would benefit from greater representation of opposing views, Teutsch supported holding off on voting to finalize the recommendations until dissenting opinions were incorporated.

"We want to make sure that the issues that are raised by those who have perspectives that differ from the final recommendations, we need to have those comments in here," Teutsch said. "We need comments from people in writing. We have tried to get them in the past and we have not received them.

"Clearly, our recommendations will not be universally welcomed," Teutsch continued. "We need to make sure we are laying out the rationale for these relations and why they were made."

The committee is planning to hold a public teleconference by year end to vote on the final recommendations. The report is slated for release in early 2010.

'Unintended Consequences'

The committee's recommendations hinge on its finding that there is no way to "invent around" a patent on a genotype/phenotype association or a specific gene sequence. As a result, SACGHS found, gene association patents and exclusive licensing practices have harmed patient access to genetic testing in geographically isolated and poor populations.

Furthermore, the committee found "no consistent findings by case studies or public comments that patents were necessary to stimulate research which leads to the availability of genetic testing."

If anything, patents on genes diminish public knowledge, since they discourage follow-on research, and compromise patient safety by restricting second-opinion testing, the committee reported. Non-exclusive licenses and exemptions on gene-association patents would encourage more competition and improve access and the quality of tests, the committee argued.

Moreover, with the introduction of new sequencing and multiplex tests promising to increase the speed of genomic advances and decrease costs, the committee said that gene patents would be a deterrent to innovation, since they would require developers to acquire multiple patents for a single test.

These conclusions by the task force appear to be in line with the American Civil Liberties Union's position on gene patenting. In May, the ACLU filed a lawsuit on behalf of four scientific organizations — representing more than 150,000 medical professionals, researchers, women's health groups, and individual women — alleging that the BRCA gene patents held by the University of Utah Research Foundation and exclusively licensed to Myriad "stifle research that could lead to cures and limit women's options regarding their medical care."

Specifically, the lawsuit asserts that Myriad's exclusive license on the BRCA1 and BRCA2 genes, linked to increased hereditary risk for breast and ovarian cancer, violates the First Amendment by restricting research and knowledge [see PGx Reporter 05-13-2009].

Another pending lawsuit that will have an impact on gene patenting is Bilski v. Kappos, which is currently being decided by the Supreme Court as to whether a "business method patent" for hedge fund trading not associated with a machine, and that did not transform any physical article, is a patentable subject matter.

Committee members and presenters who disagreed with the committee's conclusions urged the task force to hold off on proposing congressional action and statutory changes to patent law until these cases are decided.

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"The landscape of patent law is presently in flux with pending litigation at a variety of levels, including the Supreme Court," Walcoff told Pharmacogenomics Reporter. "Determinations of patentable subject matter are being worked out by the courts and the recommendations for broad statutory exclusions seem premature."

Michael Remington, a partner in the law firm Drinker, Biddle & Reath and counsel to WARF, made similar comments during the public period of the meeting. "As regards the relationship between the courts and Congress, generally speaking, Congress waits for definitive court decisions before it legislates," Remington said.

The non-profit WARF manages IP for the University of Wisconsin-Madison under the auspices of the Bayh-Dole Act of 1980, which gives US universities, small businesses, and non-profits the right to patent their inventions resulting from government funding.

One of the committee's recommendations would encourage the government to limit the granting of exclusive licenses for those entities patenting inventions under the Bayh-Dole Act. In a presentation before the committee, Remington expressed his view that such action would be harmful to academic research and hinder innovations.

Remington urged the committee to explore mechanisms such as patent thickets and clearinghouses to improve patient access to genetic tests. However, the SACGHS task force's investigations were inconclusive as to the viability of such strategies in bettering patient access.

The Council on Governmental Relations, an association of more than 175 US research universities and the Association of American Universities pointed out in their statement to the committee that a patent is only one in a complex tapestry of conditions and factors that bring in investments for product development. As such, "it is critical that universities retain the flexibility to appropriately balance these multiple licensing issues and to explore creative solutions to emerging problems," the groups said.

"Many of the recommendations in the report, however, are directed toward holding universities accountable to quasi-standards, leaving no ability to address case-specific and compelling circumstances," the groups stated, adding that many of the committees recommendations are based on older practices and do not reflect current, evolving norms.

In a statement, BIO maintained that the committee's recommendations would advance a separate patent rule for genetic tests, and as such, could create a situation where other medical industries demand the same type of patent exemptions.

"The patent, licensing, and tech transfer system in this country is, by any objective measure, working quite well overall. The evidence shows that decisions about what patents to seek and how best to license them are decisions that are best made by the researchers and their commercial partners, who have the greatest incentives to achieve widespread patient access to their discoveries," BIO President Jim Greenwood said in a statement.

"Enacting these recommendations would risk thousands of jobs across the country by stifling university-industry partnerships and undermine the country's global leadership in biotech innovation."

At least one committee member agreed that the task force's recommendations were too broad and could impact other industries.

"I disagree with the assertion that the [main] recommendations … are narrowly tailored," McDermott, Will & Emery's Walcoff told Pharmacogenomics Reporter this week. "I think they are fairly broad recommendations that could have serious unintended consequences, especially with respect to investment in personalized medicine. For example, the proposed statutory changes could be read to include therapeutic biological products, not just molecular diagnostics."

With this, Robert Cook-Deegan, director of the Center for Genome Ethics, Law & Policy at Duke University, disagreed. "The recommendations are quite narrow," Cook-Deegan told Pharmacogenomics Reporter. "I think they are pretty explicit that the patent exemptions would only be for gene associations and would not impact therapeutics or instrument patents."

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However, "diagnostic-use exemptions would impact private investment on genetic tests," Cook-Deegan acknowledged, adding that the committee knew this well in issuing its recommendations. Cook-Deegan and others at the Center for Genome Ethics, Law & Policy helped gather public comments that provided the basis for SACGHS' recommendations on gene patenting and licensing practices.

What's Actionable?

Dissenting committee members questioned whether the task force's main recommendations were actionable by the HHS Secretary.

"What charge does the Secretary have in discharging these recommendations?" committee member Marc Williams, director of the Clinical Genetics Institute at Intermountain Healthcare, posited.

In Cook-Deegan's view, while some of the recommendations may require statutory changes, "that is no reason for the committee to not submit these recommendations."

After all, "the HHS Secretary isn't the only person that is going to be looking at this report," Cook-Deegan pointed out. "Other secretaries in other government divisions will be looking at this report, too."

Cook-Deegan asserted that the value of the committee's report lies in that no other group has taken the time to investigate gene patenting so extensively in the past.

Still, dissenting members, among them Walcoff, urged the committee to put forth recommendations that are more in line with the HHS secretary's charge and try to find alternative avenues for improving patient access.

One option discussed during the meeting was whether changing the Centers for Medicare & Medicaid Services' reimbursement practices would improve access for indigent populations. The committee's investigations found that while "generally" patient access to genetic tests is not affected when gene associations are patented, access problems do arise when sole providers of a particular test fail to secure coverage from payors. This access gap often occurs for "indigent populations" covered under Medicaid.

While Medicaid's limited reimbursement for genetic tests offered by single-source labs was quickly identified as an area needing further attention, a CMS representative noted that statutory changes would be required to change current reimbursement practices.

"Most of the Medicaid coverage and reimbursement for genetic testing is done at the state level. Very few national coverage decisions are made on things like that. So … one of the things that makes it easier is if there is a reference lab that has multiple genetic tests … We want to negotiate the context but we are not going to negotiate 50 contracts," said committee member Sylvia Mann Au, the genetics coordinator for Hawaii Department of Health.

"Anything that restricts access to testing to sole-source providers, or labs that are far away, or labs that are inaccessible, there's going to be less and less chance that we are going to [have] a contract with that lab unless it's a really bad public health problem in our state," Au said.

Short of statutory changes, Cook-Deegan noted that one way of improving patient access to tests would be for academic institutions to self-regulate how they grant exclusive licenses.

One of the committee's recommendations urges for the HHS Secretary to promote voluntary adherence to best practices licensing guidelines put forth by the National Institutes of Health and the Organization for Economic Co-Operation and Development. Also, the Secretary should convene stakeholders to develop a code of conduct that will "enable broad access to such technologies," the committee recommends.

Show Me The Evidence

One of the charges from dissenters was that there was a lack of evidence supporting the committee's recommendations.

"The 77 public comments show no consensus regarding systemic problems with access to genetic testing caused by intellectual property," Stanton, the ad hoc expert on the SACGHS gene patenting task force, said in a statement.

"While some individuals and a few organizations state that genes should not be eligible for patenting," he noted that most organizations, including the Association of University Technology Managers, the American Association of Clinical Chemistry, the American Association on of Medical Colleges, and BIO "state or imply that the report scope is too broad and that there is no evidence of access problems meriting significant legislative or practice changes."
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Stanton maintained that "different commenters suggest distinct changes, but those that have been adopted in the report represent unique or minority opinions."

Conversely, the committee reported after review of the public comments and literature that "patient access issues [particularly for the Medicaid population] were not isolated problems."

Bolstering this view is a study published in the current issue of Nature Biotechnology, which concluded that while "not many blocking gene patents exist, proposals aiming at banning patents on human genes do not provide a plausible solution, unless the ban would be on patents for broad genetic diagnostic methods."

The study was authored by Isabelle Huys, Nele Berthels, Gert Matthijs, and Geertrui Van Overwalle at the Catholic University of Leuven in Belgium. The study was paid for by the Fund for Scientific Research in Belgium and EuroGentest, a five-year project supported by the European Union to standardize genetic testing regulations in Europe.

The report gives the example of the European Society of Human Genetics in Vienna, which recently recommended avoiding patenting of the pure link between a mutation and disease.

In this regard, Cook-Deegan suggested that perhaps it was industry critics who lacked the evidence to claim that limiting gene association patents would harm innovation. "The patent system hasn't collapsed in a heap in France and Belgium, and they have very similar diagnostic-use exemptions," Cook-Deegan pointed out.

In line with SACGHS' recommendations, the Nature Biotech article suggested that "more attention be paid" to "responsible" licensing practices.

"Otherwise, the risk exists that the control by owners of patents containing those broad claims with respect to genetic diagnostic testing may in the future dissociate actual genetic diagnostic testing from genetic counseling and clinical investigation, which is to the detriment of progress of the genetic diagnostic service and public healthcare system," the study authors warned.

The Scan

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Still Some SARS-CoV-2 Sequencing Holes

The Wall Street Journal reports that viral genomic surveillance has improved in the US, though says there are still gaps.

Avoiding Passing Them On

People with known disease-linked genetic variants are turning to in vitro fertilization so as to not pass those variants to their children, the Washington Post says.

PNAS Papers on Long Cell-Free DNA in Maternal Plasma, Genetic Propensity for Voting

In PNAS this week: long, cell-free DNA of maternal and fetal origins identified in maternal plasma, and more.