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Emory University, Georgia Institute of Technology, Roche

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Emory Scientist Develops New Oligo-Based Biosensors to Aid Cancer Drug Development

A researcher at Emory University and the Georgia Institute of Technology has developed a new kind of biosensor that allegedly can recognize and detect specific DNA sequences and genetic mutations in certain laboratory experiments, according to a report by Emory University.

The researcher, Shuming Nie, professor of biomedical engineering in the Coulter Department of Biomedical Engineering at Emory and Georgia Tech, said the technology could lead to a new method of cancer detection and drug development.

To develop his so-called “smart nanoparticle probes,” Nie attaches oligonucleotides to 2.5-nm gold nanocrystals, which he said act as scaffolds and as quenchers for fluorescence. The oligos are then labeled with a fluorescent dye at one end and a sulfur atom at the other end.

“When a nanoparticle probe binds to its target molecule, an energy transfer causes the quencher to be suppressed and the particle to illuminate,” Emory said in a statement that announced a presentation Nie made at the 225th national meeting of the American Chemical Society last week.

“Nie believes the new nanoparticle probes will be more effective than conventional molecular beacons because their unique shape is better suited to binding with target molecules, and because their fluorescence changes very little with changes in temperature.”

According to Emory, the particles “might be able” to profile a large number of genes and proteins simultaneously, allowing physicians to individualize cancer treatments based on the molecular differences in the cancers of various patients.

“Because of their novel structural and optical properties, these nanobeacons open new opportunities in biomolecular sensing and bioengineering,” the school said in a statement.

Nie “hopes to use the nanoparticle beacons to trace specific proteins in cells” for early cancer diagnosis, and to monitor the effectiveness of drug therapy. He also “plans to use the particles to quantify and identify gene sequences, proteins, infectious organisms, and genetic disorders,” according to the statement.

Said Nie: “We expect that the integration of nanotechnology with biology and medicine will soon produce major advances in molecular diagnostics, therapeutics, molecular biology, and bioengineering.”

— KL


Roche Taq Polymerase Patent Case Sent Back to Lower Court

A US federal appellate court earlier this week sent back to a lower court a patent-infringement suit between Promega and Roche over the Taq DNA polymerase used in PCR and gene sequencing.

While the ruling of the US Court of Appeals for the Federal Circuit does not end the 11-year dispute between the two companies, Promega views it as a favorable ruling. In response to the decision, the company issued a statement saying that it is “pleased with the findings by the court of appeals. … Promega remains confident in the ultimate favorable outcome.”

Roche had appealed a decision by the Federal District Court in December 1999 that ruled in favor of Promega and found the disputed patent, US 4,889,818, unenforceable. At the time, Judge Vaughn Walker of the Northern District of California in San Francisco concluded that the patent was obtained by fraud and that Roche had intentionally withheld material information and distorted important facts in obtaining the patent.

This week’s ruling wraps up deliberations by the circuit court that began with an appeals hearing in May 2001.

The judges examined the district court’s ruling, which found Roche guilty of “inequitable conduct” based on three categories: representations proving the effectiveness of a procedure described in the patent; representations concerning the “comparative fidelity and template dependence” of the Taq enzyme and the prior art enzymes; and representations regarding the difference in molecular weight between the claimed and prior art Taq enzymes.

Two out of three of the circuit-court judges upheld the first two rulings by the district court and reversed the third. The dissenting judge argued in favor of overturning all three findings by the district court.

“An important step in the judicial resolution of inequitable conduct claims is for the court to determine whether the material misrepresentations or omissions in question are sufficiently serious in light of the evidence of intent to deceive, under all the circumstances, to warrant the severe sanction of holding the patent unenforceable,” wrote the circuit court judges. “In this case, the trial court did not expressly address this step in the inequitable conduct analysis.”

Roche and Promega are engaged in similar litigation in Europe and Australia. The Roche Taq patent is currently considered invalid in both regions, where appeals by Roche are currently pending.

— BT

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