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International Therapeutics Outlicenses RNAi Quantitation Technology to Rosetta

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Converting a beta tester into a customer is key for any company with a new technology, and International Therapeutics has managed to do just that.

The company said this week that it has non-exclusively licensed its ProxiQuant oligonucleotide quantitation technology to Rosetta Inpharmatics for use in detecting siRNA in its genomics research efforts.

The deal marks the second time ITI has licensed the technology, which was developed out of an RNAi-based therapeutics collaboration with John Rossi and the City of Hope, and another step towards the establishment of an important source of revenue for the development-stage drug developer.

ProxiQuant is an enzymatic application that allows the stoichiometric generation of surrogate DNA targets from primary RNAi molecules, such as siRNAs, in biological samples, according to ITI. “It can [also] be applied to microRNA; it can be applied to any small oligonucleotide that has a limited base length of 20 bases,” Omar Haffar, president and CSO of ITI, told RNAi News this week.

“It’s a quantitative method that can measure down to 50 to 100 copies of siRNA per cell,” he added, noting that ProxiQuant is non-radioactive — an important consideration for groups that either don’t want to work with radioactivity, or are not licensed to do so.

“In developing siRNA in genomics or as therapeutics, you need to be able to identify your biological inhibition, and relate it back to siRNA concentration to correlate the biologic effect with the amount of siRNA in your sample,” Haffar said. “So far, there really isn’t a method to do that; people have been using hybridization with radioactive probes … but [this] is … labor intensive … and is radioactive.”

Indeed, the need for an easy and safe way of detecting siRNAs and other small oligos appears to be a priority for the industry. Recently, Ambion senior scientist Emmanuel Labourier told RNAi News that his company is working on similar technologies (see RNAi News, 9/3/2004).

Describing how ProxiQuant works, Haffar said that “you hybridize … small oligos to … siRNA. Then, we [add] extensions on the oligos that we’ll call other sequences that are non-mammalian,” he said. “Basically, you do [DNA-RNA] hybridization with your siRNA, then you ligate the oligos at the point where they meet.

“You’ve generated a longer proxy strand … that is bigger due to the outside extensions, [and] you use that proxy molecule of DNA … to give you a direct measure of how much siRNA you had,” he said. “In order to generate the proxy DNA strand, it would be equivalent to one siRNA, so by quantifying your proxy DNA, you are actually quantifying directly how much siRNA you had in the sample.”

Mother of Invention

ITI developed ProxiQuant in order to solve a problem encountered by the company and Rossi in developing siRNA-based treatment for HIV, according to Haffar.

“In our collaboration, we came to the conclusion that when you look at viral inhibition inside a cell infected with HIV in the presence of siRNA, and you record the biological effect, it’s important to be able to show that the dose response of your input siRNA correlates with the inhibition of HIV,” he said.

The collaboration between ITI and Rossi was using siRNAs expressed by DNA vectors, and Haffar said that they wanted to be able to confirm firstly that the siRNA was being expressed following vector transduction, and secondly that increased siRNA expression correlated to HIV inhibition.

“In order to do that, we had to develop a method to quantitatively identify within our cell samples the amount of siRNAs being expressed,” Haffar said. “That’s where ProxiQuant came from. It was a method developed from our need to identify expression of siRNA, and it worked so well … we started talking to companies about … putting it out into the market.”

According to Haffar, Rosetta had been evaluating a preliminary version of ProxiQuant, and its decision to take a license is an important validation of the technology.

The licensing agreement is also key for ITI because it is the first time it is able to publicize industry interest in ProxiQuant. According to Haffar, a tertiary tester had previously taken a nonexclusive license for applications that include but are not limited to siRNA. However, that licensee has not yet given ITI permission to publicly announce the deal.

Haffar said that ITI is currently in discussions with other possible licensees, and is also considering striking a deal with a collaborator through which the ProxiQuant technology could be made available as a kit.

“We would provide an exclusive license to a [party] that’s interested in generating a kit for ProxiQuant,” he said. “Once that happens, when people start buying the kit, they get an automatic non-exclusive license to use the technology without having to come to us. We have some discussions ongoing [with potential kit developers], but we would welcome anybody interested in discussing this further with us.”

In the meantime, ITI is primarily focusing on developing a nuclear entry inhibition technology and generating revenue through ProxiQuant, having stepped back from its own RNAi therapeutics work, at least for awhile. Currently, ITI provides its ProxiQuant technology to Rossi — who is a member of ITI’s scientific advisory board — to support his efforts to develop RNAi-based HIV therapeutics. The company has no active role in the actual research, however, Haffar said.

Rossi’s work is part of a broad project being funded by the National Institute of Allergy and Infectious Diseases focused on developing gene therapies for HIV. In addition to the several academic researchers contributing to the initiative, Benitec is developing RNAi constructs that target multiple sites of HIV, Rossi told RNAi News.

Haffar noted that ITI had discussions with Benitec about establishing a partnership, but these negotiations have since ended.

Despite its limited role in the NIAID-funded project, ITI does have the option to take an exclusive, worldwide license to any RNAi-based anti-HIV technology applied to T-cells resulting from Rossi’s work, leaving the door open for future RNAi drug programs, Haffar said.

“Maybe in a year or two, through this collaboration with City of Hope, we may go back and [begin] a big effort in RNAi,” he said. “But at this point, our small molecule development [program] takes a lot of money.”

— DM