Sequenom, Stanford Stake IP Claims for Sequencing-Based Prenatal Test Methods
A new paper by researchers at Sequenom and the Chinese University of Hong Kong is confirming the feasibility of using high-throughput sequencing of fetal and maternal DNA in a mother’s blood as part of a non-invasive prenatal test for Down syndrome. But with it come new questions over intellectual property related to the test.
In a paper that’s scheduled to appear online this week in the Proceedings of the National Academy of Sciences, Chinese University of Hong Kong researcher Dennis Lo led a team of investigators who demonstrated that they could use massively parallel DNA sequencing to detect Down syndrome from cell-free fetal DNA in pregnant women’s blood. The researchers pinpointed more than a dozen Down syndrome pregnancies — regardless of whether the women had previously undergone invasive testing.
The publication is the latest in a string of papers covering the development of prenatal genetic tests that do not rely on the use of invasive procedures such as chorionic villi sampling or amniocentesis, which carry a small miscarriage risk.
But it is not the first to report on the use of genomic sequencing of maternal blood samples for prenatal Down syndrome diagnosis. This October, a team of researchers from Stanford University led by Stephen Quake published a paper in PNAS demonstrating that they could detect fetal Down syndrome and other trisomies by sequencing fetal and maternal DNA in a mother’s blood sample and assessing the relative amount of sequence from each chromosome.
The intellectual property landscape surrounding the technologies is uncertain given that both teams have claimed patents related to the techniques described in their respective papers.
Seven authors on the Lo-led paper have reportedly filed patent applications related to the detection of fetal nucleic acids in maternal blood using non-invasive techniques. Sequenom said this week that it has recently licensed exclusive rights to the massively parallel genomic DNA sequencing test used in the Lo-led study.
Meanwhile, Quake and co-author Christina Fan, also at Stanford, filed for a patent related to the technology used in their own paper. “I think everything in this [new Sequenom] paper is covered by my patent,” Quake told GenomeWeb Daily News.
Separately this week, Fluidigm announced that it has secured co-exclusive licenses to the Stanford researchers’ approach for assessing fetal genetic characteristics from fetal DNA in maternal blood using digital PCR and high-throughput sequencing. The licenses reportedly cover the use of fetal genetic screening by digital analysis, non-invasive fetal aneuploidy diagnosis by sequencing, and digital PCR-enabled prenatal diagnosis.
Quake, who is a co-founder of Fluidigm and chair of its scientific advisory board, said that Fluidigm and a prenatal diagnostic company that did not yet wish to be identified had obtained co-exclusive licenses to the IP.
Fluidigm spokesman Howard High told GenomeWeb Daily News that the company took the opportunity to secure rights to an important piece of intellectual property as part of its ongoing effort to make sure that its customers have access to important research tools.
He said he believes the whole area of non-invasive prenatal research has the potential to benefit families worldwide. But High emphasized that Fluidigm’s current focus is on providing tools to those involved in various kinds of research. “We’re a company right now that services researchers,” he said. “We’re not a diagnostic company as such.”
Meanwhile, Charles Cantor, Sequenom’s CSO and co-author on this week’s PNAS paper, told GenomeWeb Daily News that Sequenom’s patents, based on Lo’s research over the past decade or so, “cover the application of circulating fetal RNA and DNA for the purposes of non-invasive prenatal testing regardless of the platform used.”
In their October publication, Quake and his team used Illumina Genome Analyzers to sequence DNA from the blood of 18 pregnant women. They found that they could detect fetal chromosomal abnormalities, including trisomy 21, trisomy 13, and trisomy 18, in a mother’s blood as early as 12 to 14 weeks into pregnancy.
For the latest paper, Lo, Cantor and their colleagues took their own crack at genomic sequence-based prenatal testing. While Cantor said that the “principle is pretty much the same” as that used in the Quake paper, he noted that “the protocols are different.”
After determining that they could indeed detect and sequence fetal DNA from maternal blood samples in pregnancies involving both male and female fetuses, Lo and his team tested the approach specifically for trisomy 21, assessing blood samples from 28 pregnant women — 14 carrying Down syndrome fetuses and 14 carrying euploid fetuses.
They obtained blood samples from each of the women during their first or second trimester, did massively parallel sequencing with an Illumina Genome Analyzer and aligned the sequences using the ELAND software package to determine the chromosomal origin of each sequence. The team then counted the number of reads from each chromosome and looked for over-representation of chromosome 21, indicating trisomy 21.
Lo and his team detected all of the trisomy 21 pregnancies regardless of whether the mother had already undergone an invasive procedure such as amniocentesis. These results were independently confirmed by karyoptyping.
The major difference between the papers, according to Sequenom, is that the latest research establishes the effectiveness of a non-invasive, massively parallel genomic sequencing test before any invasive procedures, such as amniocentesis. In contrast, the Stanford paper relied on blood samples taken from women who had undergone such procedures relatively recently — which Cantor said may have artificially increased the level of circulating fetal nucleic acids in the women’s blood.
“I think that’s a lot of sleight of hand,” Quake said. He argued that the amount of cell-free fetal DNA he and his team found in maternal blood was not substantially higher than that reported in other papers. “There’s no significant variation.”
The teams also disagree about the diagnostic role for sequencing-based prenatal tests. Although Cantor said the method works very well and is a “wonderful academic achievement,” he said it is still too expensive to use diagnostically.
According to Lo and his co-authors, the cost of sequencing reagents was $700 per sample with an output of 16 samples per week per Illumina instrument. Though both cost and sequencing time are expected to decrease, Cantor said the sequencing-based tests are as much as three years behind non-invasive tests currently being evaluated in a clinical setting.
Sequenom is currently testing its SEQureDx test, which uses Sequenom’s mass spectrometry platform to diagnose trisomy 21 from fetal RNA in maternal blood. If clinical trials are successful, the company plans to commercialize that test next June. The SEQureDx approach is currently several orders of magnitude cheaper than sequencing-based testing, according to Cantor.
The company recently announced that Brown University researchers are starting a 16-month, 10,000 person study of SEQureDx technology for detecting Down syndrome in the first trimester of pregnancy. And Cantor anticipates at least two large clinical trials of the SEQureDx platform, one in which Sequenom researchers are not involved and another, an in-house study, that will help the company get its CLIA lab up to speed.
For his part, Cantor speculated that the massively parallel genomic sequencing test could eventually complement more cost-efficient tests such as SEQureDx. For example, he said, sequencing may eventually be used to assess the roughly five to seven percent of cases that are inconclusive following SEQureDx testing.
Quake disagrees. Sequencing is the clear way to do non-invasive prenatal testing, he argued. “I think this will become the diagnostic.” He claimed existing noninvasive Down syndrome tests are not very informative and provide variable results depending on the ethnicity of those taking the test.
A clinical study on the sequencing-based method for prenatal diagnosis is ongoing at Stanford University, Quake added. It involves several hundred patients and researchers plan to expand the scope of the study. For example, Quake said they plan to compare Helicos BioSciences' sequencing technology with the Illumina platforms already being used.
Quake, a co-founder of Helicos, said the goal is to begin testing Helicos' Heliscope for prenatal diagnostics within the next month or so.
But while Quake believes sequencing-based, non-invasive tests will be used diagnostically within three years, Cantor predicted it will take longer. Between now and then, Cantor said, “There will be time to sort out the patent issues, if there are any.”
— Andrea Anderson
Cellular Dynamics Gets $18M in Financing, Merges with Other UW Spinouts
Stem cell research tools company Cellular Dynamics International, a spinout of the University of Wisconsin-Madison, said last week that it has closed an $18 million Series A financing round and merged with two sister UW spinouts, Stem Cell Products and iPS Cells.
The round of financing was led by Tactics II Stem Cell Ventures and by the Wisconsin Alumni Research Foundation. The new company will continue to operate under the name Cellular Dynamics International.
Financial terms of the merger were not released.
CDI was founded in 2004 by UW researcher James Thomson and UW colleagues Craig January, Timothy Kamp, and Igor Slukvin, as well as by Tactics II Ventures. Thomson is also a co-founder of Stem Cell Products and iPS Cells.
CDI is commercializing pluripotent stem cell-derived heart cells and other cell types for use by the pharmaceutical industry to test drugs for toxicity. The firm also said that it is establishing infrastructure for producing human stem cell types and for research to create stem cell biobanks that will use reprogramming to show the utility of banking individual stem cell lines for future use.
Cell types that the company derives from these banked stem cells will provide a basis for developing genetically diversified and personalized cell lines for therapeutic purposes and for studying potential drug reactions for individuals.
Glencoe to Exclusively Provide Commercial Licenses for UW-Madison LOCI Software
The Laboratory for Optical and Computational Instrumentation at the University of Wisconsin at Madison and Glencoe Software said last week that Glencoe will be the exclusive provider of commercial licenses for LOCI’s Bio-Formats microscopy file format converter library.
LOCI is a member of the Open Microscopy Environment Consortium. Bio-Formats is open-source software licensed under the GNU General Public License Version 3 and is used in hundreds of laboratories around the world, Glencoe said.
Glencoe is also a member of the OME Consortium, and is a development partner in the Bio-Formats project.
In a statement, LOCI Director Kevin Elicieri said that he was “pleased to announce this agreement with Glencoe Software for commercial licensing of Bio-Formats. While we are dedicated to keeping the open-source nature of Bio-Formats, this agreement ensures that commercial organizations can make use of Bio-Formats as well.”
Seattle’s Accelerator Announces Series A Investment in CIT Spinout GPC-Rx
Seattle-based biotechnology investment and development company Accelerator Corporation last month announced an undisclosed Series A investment in GPC-Rx, the second Accelerator-backed startup from the California Institute of Technology.
GPC-Rx’s technology was developed at CalTech’s Materials and Process Simulation Center, headed by William Goddard. The technology provides a method of developing novel drugs targeting G-protein coupled receptors that is expected to be cheaper than current GPCR drug discovery methods. Specifically, Goddard’s group has established and validated methods to generate predictive 3D structures of GPCRs and their complexes with known ligands, Accelerator said.
The syndicate of investors leading the Series A investment in GPC-Rx includes Alexandria Real Estate Equities, Amgen Ventures, ARCH Venture Partners, OVP Venture Partners, PPD Inc., and WRF Capital.
AVI BioPharma Exclusively Licenses IP for DMD Rx from University of Western Australia
AVI BioPharma has signed an exclusive, worldwide license agreement with the University of Western Australia for a patent application related to the treatment of Duchenne muscular dystrophy, the company said late last month.
The patent application has been filed in the US and other undisclosed countries, and claims compositions and methods for treating DMD in humans by skipping exons in the dystrophin gene using antisense oilgomers.
Among the inventors listed on the patent application is Stephen Wilton, head of the molecular genetic therapies group at UWA. AVI said in a statement that Wilton is a “longtime collaborator” of the company, and securing license to the patent application strengthens AVI’s leading position in the field of exon skipping for DMD.
The company said that the license supplements IP covering general RNA splice altering that AVI obtained when it acquired Ercole Biotech earlier this year, as well as other AVI-filed patents and in-licensed IP specific to exon skipping of the dystrophin gene as a therapeutic target.
Financial terms of the licensing deal were not disclosed.
PerkinElmer and EMBL Enter Corporate Partnership to Support Advanced Training Center
PerkinElmer and the European Molecular Biology Laboratory said last week that they have entered into a corporate partnership in support of EMBL’s Advanced Training Center in Heidelberg, Germany.
Under the terms of the partnership, PerkinElmer will sponsor and have access to the ACT’s center of excellence for molecular biology training in Europe, including scientific training programs, facilities, conferences, and events.
PerkinElmer will also provide advice regarding future programs and conferences at the ACT.
EMBL established the corporate partnership program earlier this year to create and enhance long-term, effective relationships between EMBL and corporate partners, it said.
Germany’s t2cure Acquires Patents for Characterizing Marrow-Derived Cells from Frankfurt U
German biopharmaceutical company t2cure said last week that it has acquired a family of patents and patent applications from Innovectis, the technology-transfer arm of Frankfurt University, for an undisclosed amount.
The acquired patents cover a technology that allows for the rapid characterization of the potency of bone marrow-derived cells in cardiovascular disease treatment.
The potency of stem cells characterizes their potential to induce or perform repair processes in adult tissue, t2cure said, adding that recent drafts from the European Medicines Agency and US Food and Drug Administration have made it clear that potency testing will be a key criterion for batch release and market approval of stem cell-based therapies.
Cellectricon Partners with Harvard’s ICCB-Longwood on Whole-Genome RNAi Screening
Cellectricon last week said that it is collaborating with Harvard Medical School’s ICCB-Longwood screening facility on whole-genome RNAi-screening technology.
Specifically, Cellectricon said that Harvard-ICCB-Longwood will use Cellectricon’s Cellaxess HT system, which enables high-throughput transfection for reagent-free delivery of genetic material to a wide range of cell types.
Additional details of the collaboration were not disclosed.
Singapore’s Technology Transfer Network Adds Six Members
The Technology Transfer Network, a Singapore- based alliance of tech-transfer offices, said last month that it has added six new members to the network.
The new members, announced at the inaugural TTN Innovation and Enterprise Forum at Biopolis, Singapore, are Auckland UniServices, AUT Innovation and Enterprise, and WaikatoLink, all of New Zealand; the State University of New York at Binghamton; the British Columbia Cancer Agency of Canada; and INI-GraphicsNet in Germany.
As affiliate members, the new partners will be able to share best practices, expertise, resources, and networking opportunities with existing members.
With the addition of these new members, the TTN, founded in February of this year, now has 22 members throughout Asia, the US, Canada, Europe, and New Zealand.
Cyntellect Enters Research Collaboration with University of Florida to Purify Cancer Stem Cells
Cyntellect has entered into a research collaboration with the University of Florida Interdisciplinary Center for Biotechnology Research, the company said late last month.
The agreement will focus on a variety of research areas, including the purification and analysis of cancer stem cells, rare cells which are believed to be directly involved in propagating cancer, Cyntellect said.
Under the agreement, the University of Florida will gain access to Cyntellect’s LEAP system for cell manipulation and purification, while Cyntellect will receive certain payments and commercial rights to discoveries under the collaboration.
The collaboration follows on the heels of a similar partnership with UF’s McKnight Brain Institute, announced earlier this year.
Washington’s Life Sciences Discovery Fund Announces ’09 Grant Competitions, Including New Commercialization Grants
The Washington state Life Sciences Discovery Fund last month announced its 2009 grant competitions, including its first-ever commercialization grant competition.
Funding opportunities include a project grant competition of up to $8 million in total awards; a program grant competition of up to $20 million in total awards; and commercialization grant competitions of up to $750,000 per round.
Specifically, the LSDF commercialization grants will target research efforts designed to validate the commercial merit of new technologies at Washington-based educational and non-profit research institutions. Grants of up to $150,000 will be made to eligible institutions, and industry collaboration is encouraged.
Funding for the project and program grants comes from Washington’s allocation of bonus payments from the Master Tobacco Settlement. Funding for the commercialization grant program comes from a portion of the Tobacco Settlement payments and donor funds provided by Amgen, the Bill and Melinda Gates Foundation, Microsoft, the Paul G. Allen Family Foundation, Group Health Cooperative, Safeco Foundation, and Regence BlueShield.
Requests for proposals for all of the LSDF 2009 grant competitions will be release in early January. More information about the grants can be found on the LSDF Funding Opportunities website.
NJTC and MACC to Hold Regional Commercialization Conference in Philadelphia
The New Jersey Technology Council and supporting organizations from the Mid-Atlantic Commercialization Consortium will hold a Regional Commercialization Conference on Dec. 11, at the Cira Center in Philadelphia.
The conference will bring together an audience of university tech-transfer officers, entrepreneurs, and investors to discuss technology-commercialization issues, and to present and hear presentations on the commercial prospects of specific technologies.
Speakers will include Patrick Harker, president of the University of Delaware; and Banu Onaral, professor and director of the School of Biomedical Engineering at Drexel University.
The Mid-Atlantic Commercialization Consortium comprises industry, university, and economic development representatives from New Jersey, Pennsylvania, Delaware, and New York.
CRT, Technology Partnership Ink Agreement to Market Biological Imaging Device
Cancer Research Technology Limited and the Technology Partnership have signed an agreement to commercialize lens-free imaging equipment developed by a consortium of scientists at UK research institutions.
The imaging equipment, called CyMap, was developed by members of the Optical Biochips Consortium of the Gray Institute for Radiation Oncology and Biology at the University of Oxford; Cardiff University; and Bangor University.
Intellectual property arising from this research has been assigned to CRT, which has filed a patent to protect the technology. Under the terms of last month’s agreement, CRT has awarded TTP an exclusive option to license and develop CyMap.
TTP will seek other commercial partners to develop and market a range of applications based on CyMap, either by direct licensing or through co-development partnerships. CRT and TTP will share any revenues arising from future development and sales of the technology.
CyMap is able to detect a range of particle types in a solution and could be useful as part of cost-effective medical diagnostic systems to detect, quantify, and analyze medical samples such as blood or bacteria.
The technology is based on the principle that when illuminated using a simple light source, objects such as cells or pathogens in a sample create light diffraction and interference patterns that can be recorded by a CCD camera and analyzed using computer algorithms.
CRT is a specialty commercialization and development company that is a wholly owned subsidiary of Cancer Research UK. TTP is an independent technology and product development company based in Melbourn, UK.
NanoVector Licenses Plant Virus Drug-Delivery System from NC State
Early-stage biopharmaceutical company NanoVector said this week that it has licensed a plant virus nanoparticle drug delivery system from North Carolina State University.
The most important property of the technology, developed by NC State professors Stefan Franzen and Steven Lommel, is a built-in sensor-actuator system that may minimize the toxic side effects associated with free anti-cancer drugs in the blood stream that attack healthy cells, NanoVector said.
The technology “will finally provide the highly sought after selective targeting of tumors and intracellular delivery of anti-cancer agents for improved efficacy and fewer unpleasant side effects,” Albert Bender, NanoVector CEO, said in a statement.
Additional terms of the licensing agreement were not disclosed.
In September, NanoVector, based in Raleigh, received a $147,000 Small Business Research Loan from the North Carolina Biotechnology Center to continue developing its nanovirus vector for use as a chemotherapy delivery agent (see BTW, 9/24/2008).
Intradigm Announces Issuance of UMass Patent for RNAi Silencing
RNAi therapeutic developer Intradigm said this week that the US Patent and Trademark Office has issued US patent no. 7,459,547, entitled "Methods and Compositions for Controlling Efficacy of RNA Silencing."
The issued patent is based on research conducted by Philip Zamore, chair of biomedical sciences and professor of biochemistry and molecular pharmacology at University of Massachusetts Medical School.
The patent generally claims methods of enhancing the RNA silencing activity of an RNAi agent through certain structural modifications in various cell types, including mammalian. The patent issues from a portfolio of several applications disclosing efficacy-enhancing methods and structural elements of RNAi therapeutics that Intradigm has exclusively licensed from the University of Massachusetts Medical School.
Intradigm said that its RNAi IP portfolio includes key assets licensed from both the UMass Medical and the Massachusetts Institute of Technology.
Mann Foundation Launches New Website
The Alfred E. Mann Foundation for Biomedical Engineering, a philanthropic organization created by billionaire Alfred E. Mann to support university-based commercialization efforts, this week announced the launch of a new website.
Features of the web site include an overview of the Alfred Mann Institutes for Biomedical Development at the University of Southern California; Technion in Haifa, Israel; and Purdue University.
The new site also provides the background and accomplishments of Mann; and a ‘Commercialize Your Idea’ section, which provides insight into the developmental steps for a biomedical technology including proof of concept, FDA regulatory approval, reimbursement strategies, and technology licensing considerations, with an emphasis toward researchers involved in this space.