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Sequenom Licenses ‘Third-Gen’ Sequencing Tech from Harvard; May Need More IP from BU

Sequenom said last week that it has exclusively licensed intellectual property from Harvard University as part of its plan to enter the highly competitive market for next-generation DNA sequencing technology.
Harvard may not be the only school to benefit from the deal, however, as the lead inventor of the technology has since moved on to Boston University, and garnered millions of dollars in funding to develop a higher-throughput version of the technology that Sequenom will likely need to license to achieve its goal.
Under the terms of the agreement, Sequenom has licensed a portfolio of patents and patent applications covering technology developed by Amit Meller, a former senior fellow at Harvard’s Rowland Institute.
The technology enables the readout of single DNA molecules by the simultaneous optical probing of multiple nanopores. Sequenom said it plans to use the technology to develop a so-called “third-generation” single-molecule nucleic acid analysis instrument that would allow a human genome to be sequenced for less than $1,000.
Financial terms of the agreement include undisclosed up-front licensing fees, milestone payments, and royalties on future products. As per Harvard’s faculty royalty sharing policy, as stated on its website, Meller and the other members of his research group at the time will receive at least 25 percent of the first $50,000 in future royalty payments and 35 percent if royalties exceed that amount.
The patents specifically cover a technique known as nanopore-based single-molecule readout technology, in which single strands of DNA are passed through nanometer-scale pores and analyzed using a combination of electrical and optical sensing.
Much of the research leading to the development of that technology was funded through a two-year, $600,000 grant, awarded to Meller in 2004, as part of the National Human Genome Research Institute’s “$1,000 Genome” grant program.
Last year, Meller left Harvard to take a position as an associate professor of biomedical engineering at Boston University. In October of last year, he was awarded a three-year, $2.2 million NHGRI grant to further develop his single-nanopore DNA sequencing technology into one based on nanopore arrays.
Meller’s group has an existing industrial collaborator in Norwegian biotech firm LingVitae, which supplies the team with DNA-preparation products that purify DNA from samples and convert it into more easily readable code units called design polymers.
Meller said that his group will continue to collaborate with LingVitae on this aspect of the technology. It is unclear whether Sequenom has licensed or will license IP from LingVitae in this area, although Charles Cantor, Sequenom’s chief scientific officer, told BTW sister publication InSequence that the possibility existed for such a scenario.
According to Meller, he and his colleagues used the first NHGRI grant to demonstrate the basic principle of the nanopore-based readout technology using single nanopores or a few nanopores simultaneously.
Now, armed with new funding, Meller and colleagues at BU will attempt to ramp up the technology to a throughput high enough to break the $1,000 genome barrier.
“The difference is that we will work on showing that these ideas will work on solid-state supports – nanopores made in a very thin film of silicon nitrite,” Meller told BTW last week. “We can make arrays of many nanopores, and we would like to show that we can read those pores simultaneously, which means that we can increase the throughput by orders of magnitude, and for us that’s a crucial thing. For any single-molecule method to achieve the goal of the $1,000 genome, it needs to be extremely efficient and fast.”
It is unclear exactly which patents or patent applications are included in the portfolio licensed by Sequenom from Harvard. Meller said that the portfolio may have covered patents based on the preliminary work done at Harvard, such as US Patent Nos. 6,362,002 and 6,673,615; as well as some earlier issued patents covering the nanopore technology.
Sequenom negotiated the agreement with the Harvard Office of Technology Development.
“Sequenom did very thorough research [for] over a year looking at the different aspects and the possible difficulties with our technology, and what it needed to bring it to some success before they made the decision to license it from Harvard,” Meller said. “During this time we stayed in relatively close contact – they called often, I visited several times, and they sort of followed up on our progress. That was without them committing anything to us – it’s just that they were interested.”

“They need the license from Harvard, but they cannot do much with that license without the expertise in our lab.”

Meller said that the main advantage that Sequenom saw in his technology is its potential throughput, which he says exceeds all polymerase-based detection methods that are either in the market or under development. “At the same time, our method may require [fewer] enzymes, which are expensive. We think this can potentially bring the cost down to a much lower level.”
Meller added that in comparison to many of the other technologies being developed under the “$1,000 Genome” grants from NHGRI, his team’s technology has already passed the basic proof-of-principle stage and is ready to be ramped up into a working system.
The main challenge now, according to Meller, is to show that the platform is working “fast and reliably, and that we have a low level of error,” which is a frequent problem with single-molecule methods.
“It’s just a matter of work, just a couple of years,” Meller added. “I don’t see a main roadblock that would force us not to continue. On the contrary, every day we find new possibilities; we can improve the biochemistry a lot by doing different processes, and I’m quite optimistic.”
As such, Sequenom is likely not through collaborating with Meller or licensing IP based on his research. Meller told BTW that since moving to BU, the school has filed additional IP based on his work, “some of which may be relevant to the sequencing technology, and some of which may be relevant to other genomic work.”
Sequeom’s Cantor told In Sequence last week that if intellectual property filed by BU was pertinent to the development of its next-gen sequencing technology, that Sequenom would “of course” attempt to negotiate a licensing deal with the school.
“Actually, we are very, very conscious of IP at Sequenom,” Cantor said. “What enabled us to be successful in the mass spec area, and now in prenatal diagnostics was to have tremendously brought patent protection. Rest assured, we examined the IP space extremely carefully before deciding to take these licenses.”
Meller added that in his opinion, Sequenom “understands very well” that there are really two components to their collaboration, one encompassing Meller’s work under the first grant at Harvard and one encompassing his current work at BU.
“They need the license from Harvard, but they cannot do much with that license without the expertise in our lab,” he said. “Therefore it is really a collaboration that we need to now continue between my lab and Sequenom. We have been talking a lot about possible ways to collaborate, and they are negotiating with BU to continue our research. But definitely we are interested in a very close collaboration between Sequenom and our research here.”
Furthermore, Sequenom’s Cantor is also a professor of biomedical engineering at BU and a professor of pharmacology at the BU School of Medicine, but is currently on a leave of absence as Sequenom’s CSO. He is also a longtime acquaintance of Meller’s, so a relationship was in place even before Meller moved on to BU.
It is also possible that Harvard and Boston University will pen an inter-institutional agreement that would allow BU to be the sole manager of Meller’s nanopore-based sequencing IP, although neither institution has indicated that such an arrangement is in the works.
Larry Schlossman, director of business development at Harvard’s OTD, told BTW that such arrangements are common when a researcher moves from one school to another and continues research that generates significant IP.
“In my experience, what usually happens is [that] the tech-transfer office at the school that the [the researcher] goes to will contact the school he departed from and engage in a discussion,” Schlossman said. “Usually it leads to some sort of an understanding, and the ultimate objective is to hopefully enter into a mutually beneficial agreement.
“The initiative for that usually – but not 100 percent of the time – comes from the school that the investigator is going to, and is usually instigated by the investigator,” Schlossman said, adding that he was unaware whether such an initiative had been suggested in Meller’s case.
A representative for the Boston University Office of Technology Development declined to comment on the possibility of such an arrangement.
Sequenom could also play a part in this process in the interest of condensing its licensing activity from two to one of the universities. Schlossman said such a scenario is not unheard of, but Sequenom had made no such indication at this time.

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