This story has been updated to include information from a June 7 open letter from Vizgen to its customers.
NEW YORK – Harvard University and George Church, one of its professors and a cofounder of numerous biotechnology firms, allegedly broke promises made in a 2009 grant proposal to openly license spatial genomics technologies developed with $19 million in funding from the National Institutes of Health.
That's the argument advanced in recent court filings from Vizgen and NanoString Technologies as part of their defenses in separate patent infringement lawsuits launched against them by 10x Genomics and Harvard. 10x acquired exclusive rights to inventions covering spatial analysis technology, specifically in situ analysis methods, as part of its $350 million purchase of ReadCoor, a Church lab spinout, in 2020.
"In the grant application, Church and Harvard committed to provide open source and non-exclusive rights for all innovations arising from the NIH funding" — $19 million over five years for the Center for Transcriptional Consequences of Human Genetic Variation (CTCHGV), Vizgen, itself a Harvard spinout, wrote in an April 25 filing with the US District Court for the District of Delaware. "This is the exact opposite approach of what Church and Harvard did in reality."
NanoString soon followed with similar allegations in a May 1 court filing, suggesting that the information in the grant documents should prevent 10x from obtaining an injunction in the US against NanoString's CosMx spatial analysis products and that NanoString should be provided a license to the technology. Last month, a German court awarded 10x an injunction against the sale of the CosMx instrument and RNA analysis reagents in that country.
10x and Harvard have argued that they are not legally bound by the text of a grant proposal. "NIH grants are not contracts," the plaintiffs wrote in a response to Vizgen filed May 18. Furthermore, neither 10x nor ReadCoor would have been party to any such agreement, they said. "Vizgen conflates NIH regulatory requirements concerning the sharing of data and materials (or 'research tools') with Harvard's practices to encourage commercialization of federally funded discoveries through patent licensing," lawyers for 10x wrote.
Church defended the course of action that led 10x to hold exclusive rights to his inventions. "'To pursue open licensing' is very different from a 'promise to only do open licensing,'" he said in an email. "For example, if only one company seems interested and only if exclusive, then the choice is not 'exclusive vs shared' but 'yes, or no product available.' The latter doesn't seem to be in the best interest of the research community."
"The risk of making such an R&D commitment is hard to make without the protection of exclusivity," he added.
The allegations raise tensions in the legal battle over technologies that enable high-resolution spatial biology, a burgeoning market that could be worth billions of dollars. In addition to the US suits over the Church lab patents, 10x has alleged that NanoString's GeoMx Digital Spatial Profiler infringes on other patents the firm controls. Also, on June 1, 10x sued its competitors in the new European Unified Patent Court.
Both Vizgen and NanoString have countersued in the US cases related to the Church lab patents. NanoString has also sued 10x for infringement of its own patents and is seeking to invalidate 10x's patents in both the US and Europe.
In a conference call with investors last month, NanoString CEO Brad Gray suggested that Church's language in the grant proposal "will reduce the probability of injunctive relief in the US by demonstrating that even [the grant recipients] believe science and the public good will be harmed by limiting access to spatial biology technologies."
Vizgen, itself a spinout from a different Harvard lab, said it was only able to obtain the full grant proposal containing the alleged promises under the Freedom of Information Act. Vizgen said Harvard fought the September 2022 FOIA request; however, lawyers for Harvard said the university produced the grant materials to Vizgen in January "in response to its specific requests" and to NanoString in April.
In the proposal — submitted to the court by Vizgen, under a section titled "Commercialization," Church and his co-investigators wrote that their proposed center "will pursue open and non-exclusive licensing agreements that encourage innovations to be made widely available to researchers and commercial entities. … More generally, we will encourage close relationships with companies who can promote broad usage of innovations by incorporating them with other technology into readily usable packages and applications."
The proposal later mentioned that "the Church Lab adheres to open-source standards to the extent possible as a matter of policy, for software, data, materials, and technology generally." Under the "Data and Materials Dissemination Plan," it said the lab had championed the concept of "open-source biology" and the "related goal … to prevent exclusive licenses from potentially interfering with technology transfer. In this regard we will try to move our technology either into the public domain or [use] non-exclusive licensing mechanisms well before they would be normally publishable."
When asked if he thought that that he followed through on the plan to pursue open licensing agreements and make the technology widely available, Church responded "Yes" but did not elaborate.
According to Vizgen's countersuit, Church and Harvard each received 10x shares worth approximately $13 million at the time, now worth about $4.4 million. The deal also made Church a scientific adviser to 10x.
Vizgen argued that the Church lab's statements were "a material condition of the grant." In its Sept. 12, 2010, award letter, NIH wrote that "compliance with the data and materials sharing and release plans … is a condition of this award. Failure to comply with these plans may result in termination of the award."
An NIH spokesperson confirmed that its award notices are "an official, legally binding document." Whether NIH has any ability to act after a grant has been disbursed is unclear. Church cofounded ReadCoor in 2016, after the grant had ended.
The 2009 grant proposal is not the only time that Church made commitments to the tenets of "open-source biology." In a proposal submitted to NIH in 2003, which led to funding for the Molecular and Genomic Imaging Center, Church wrote he would "try to move our technology either into the public domain or [pursue] non-exclusive licensing mechanisms." That proposal is publicly available on his lab website.
The resulting grant, worth at least $2 million, led to more than a dozen patents for Church and Harvard. Whether any of those patents were licensed and the terms of those licenses aren't known. Church deferred to Harvard, and the university's Office of Technology Development declined to provide information about the licensing of those patents.
Church said there were at least two instances related to DNA synthesis, in which his patents were licensed nonexclusively. Other licenses have been "split into specific sub-fields," he noted.
NIH's stance on the issues raised in these lawsuits is unclear. NIH spokespersons confirmed that award letters are considered legally binding but did not directly address questions about how important commercialization and data- and resource-sharing plans are in the grantmaking process.
Whether the Church lab's proposal contained unique language or simply broad statements that grant reviewers expected to see is also unclear.
"NIH has not assessed the frequency of including commitments regarding open licensing of inventions in grant applications, but in general, NIH data-sharing policies have not required a particular approach to licensing of inventions derived from research," an NIH spokesperson said. "Expectations for awardees related to intellectual property are provided in terms and conditions of awards, found in the NIH Grants Policy Statement and the Notice of Award."
A 2005 document titled "Best Practices for the Licensing of Genomic Inventions" states that "whenever possible, non-exclusive licensing should be pursued as a best practice." However, the document, authored by Mark Rohrbaugh, then director of the NIH Office of Technology Transfer, who is now a special adviser to the NIH on tech transfer, does afford grantees the ability to issue exclusive licenses when "necessary to encourage research and development by private partners."
In March, after obtaining the full text of the grant proposal, Vizgen sought a license to the patents-at-suit from Harvard and 10x, which was denied.
10x is not the only company with an exclusive license to Harvard-owned patents developed with federal funding, though. Vizgen itself has an exclusive license, to multiplexed error-resistant fluorescence in situ hybridization (MERFISH) technology, invented by cofounder and Harvard professor Xiaowei Zhuang and developed under an NIH grant.
In an open letter to customers on June 7, Vizgen CEO Terry Lo suggested the firm's status as a Harvard licensee should offer protection against 10x's US and European suits and that Harvard had a "conflicted role as licensor to both 10x and Vizgen."
In its US countersuit, Vizgen claimed its deal with Harvard provides an implied freedom to operate; the firm also alleged 10x infringes one of Zhuang's patents.
Whether Zhuang's grant proposal included plans about patent licensing, or promises for open licensing, is an open question. A FOIA request with NIH has not yet produced the document, though Zhuang said in an email that she recently provided her proposal to NIH to comply with the request.