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Biosearch Licenses Broad 'Non-FRET' Nucleic Acid Probe Patents from UMDNJ


By Ben Butkus

Biosearch Technologies said today that it has acquired worldwide rights from the University of Medicine and Dentistry of New Jersey to patents covering "non-FRET" nucleic acid probe technology.

Novato, Calif.-based Biosearch said that the technology will enable it to design and market new fluorescent quenched probes for quantitative PCR and highly multiplexed fluorescent probe applications. The intellectual property may also confer to Biosearch a broad patent position around many currently commercially available molecular probes, company officials said.

The probe technology was developed in the laboratories of UMDNJ researchers Sanjay Tyagi and Fred Kramer. As opposed to probes incorporating fluorophore-quencher pairs that interact with each other by Förster resonance energy transfer, or FRET, the non-FRET probes feature label pairs that interact by forming transient chemical bonds upon contact with each other, Kramer said in an e-mail to PCR Insider.

This phenomenon, known as "quenching by contact," enables a wide variety of differently colored fluorophores to be used in combination with many non-fluorescent quenchers – including novel quenchers designed to interact in this manner – thus increasing the multiplexing potential of assays incorporating the non-FRET probes.

Kramer added that many probes currently used in molecular diagnostic assays use contact quenching to help reduce fluorescence when they are not hybridized to their targets. "Because contact quenching occurs … whether there is, or is not, an overlap between the emission spectrum of the fluorophore and the absorption spectrum of the quencher, many differently colored fluorophores can be paired with the same universal non-fluorescent quencher in an assay, thereby enabling the design of multiplex assays," Kramer said.

In contrast, FRET-based probes – such as TaqMan probes; and many of the so-called molecular beacon probes also invented by Kramer and colleagues – have a "limited and finite mastery of the visible spectrum accessed by current thermocycler manufacturers and probe suppliers," Marc Beal, director of corporate development at Biosearch, said in a statement.

Kramer further noted that many current commercially available probes labeled with fluorophore-quencher pairs that were previously thought to have interacted via FRET may actually interact via contact quenching. Thus, the rights to use some of those probes "can now be provided to those that need them through a sublicense from Biosearch."

Biosearch's Beal also noted in an e-mail to PCR Insider that most multiplex qPCR reactions that contain three to five quenched fluorophore pairs will typically contain at least one non-FRET pair. Beal further commented that "many current fluorophore/quencher combinations used by the top molecular diagnostic [companies] and [in] applied markets will need the non-FRET license."

Biosearch has specifically acquired the rights to US Patent No. 6,150,097, entitled "Nucleic acid detection probes having non-FRET fluorescence quenching and kits and assays including such probes," from PHRI Properties, a wholly-owned nonprofit subsidiary of UMDNJ.

In addition, Biosearch has acquired the rights to counterpart patents in Australia, Canada, France, Germany, Great Britain, Italy, and Japan.

Biosearch has a "semi-exclusive license" to the '097 patent and its counterparts, as both Abbott and Gen-Probe have previously licensed the technology without sublicensing rights, according to Beal and Kramer. The non-FRET probes have found "widespread use in multiplex molecular diagnostic assays," Kramer said in a statement.

However, Biosearch has also acquired exclusive rights from UMDNJ to sublicense the non-FRET probe patents to companies wishing to commercialize products based on the technology.

"We are very excited to be working with UMDNJ as we again prepare to move the qPCR probe marketplace forward as we did with the Black Hole Quencher series of dyes in 2000," Beal said in a statement.

Vincent Smeraglia, director of the UMDNJ Office of Technology Transfer and Business Development, said in a statement that the school is "extremely pleased to expand and bolster our successful ongoing relationship with Biosearch Technologies and announce this new licensing partnership."

Smeraglia added that Biosearch is "the ideal partner to enable adoption of non-FRET probes technology for a wide variety of uses in biomedical applications."

Have topics you'd like to see covered in PCR Insider? Contact the editor at bbutkus [at] genomeweb [.] com.