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Alliances May Follow Invitrogen’s Acquisition of Calcium Indicator Product Lines From TEF Labs

Invitrogen intends to seek alliances with instrument manufacturers to boost sales of its calcium indicators following its acquisition last week of the Fluo 3 and Fluo 4 product lines from TEF Labs, according to a company official.
Invitrogen regained the rights to the calcium indicators after having licensed them to TEF Labs under a settlement agreement reached between TEF and Molecular Probes before the company was purchased by Invitrogen in August 2003. The Fluo 4 technology is particularly important to Invitrogen, which believes it offers distinct advantages over other indicators on the market.
As part of the deal, Invitrogen also acquired products that were developed independently by TEF Labs. “They are all fluorescent calcium indicators, and some of them have other properties that might be useful to a particular market niche,” said Vicki Singer, director of the labeling and detection technologies business segment for Invitrogen.
“Invitrogen, that is Molecular Probes, invented Fluo 4 a number of years ago,” Singer told BioCommerce Week. “TEF Labs started manufacturing and selling it, [and] there was a legal dispute between the parties that resulted in a settlement agreement, whereby TEF Labs was the only other party that was able to manufacture this material.”
She said that it was a goal of Invitrogen to get these particular calcium indicators back in house. The probes “represent one of the core technologies developed by the company and one of the core areas of expertise for the company,” said Singer.
She said that there are other calcium indicators on the market, but “most other parties that sell calcium indicators are, in fact, selling some of the weaker ones. There are a number of licensees of the University of California’s Fluo 3 patent, and they’re all selling that product. There is no other party that has a molecule comparable to Fluo 4,” said Singer.
She said Fluo 4 offers some distinct advantages over other indicators. “Fluo 4 is a perfect spectral match to the argon ion laser that’s used in high-throughput instrumentation for screening for drug candidates,” she said. Fluo 3 is not as good of a match, as it is less bright, Singer noted.
“The invention of Fluo 4 is part of a broader invention on the part of Molecular Probes of fluorinated fluorescein,” said Singer. “These are molecules that contain fluorine attached to them, and that fluorine provides them with higher brightness. In addition, it makes them more photostable, so they bleach less in the presence of light, and it makes them less pH-sensitive.”
She said as part of Invitrogen’s strategy to offer full solutions to customers, the firm “is starting to, and will be doing more, work with a number of instrument manufacturers in this area.”
The acquisition of the Fluo 3 and Fluo 4 product lines comes a week after Invitrogen said it would acquire cell-based assay company Sentigen Holding for around $25.9 million in cash (see BioCommerce Week 9/6/2006).
The firm is betting that Sentigen's Tango assay system and division-arrested assay-ready cells will help it grow its own assay-development business by providing an additional way to screen G-protein coupled receptors and other “key” drug target classes.
The acquisition “really provides us an entry into the GPCR target class market,” said Nick Ecos, vice president and general manager of Invitrogen’s Discovery Sciences Business, last week. “Our strength has been in other target classes, most notably kinases. We’re also in nuclear receptors and ion channel target classes.”
Sentigen’s Tango assay technology is applicable for GPCR targets and can also measure protein-protein interactions in living cells.

The firm “is starting to, and will be doing more, work with a number of instrument manufacturers in this area.”

Invitrogen officials declined to give a market estimate for the acquired technologies, but Ecos said, “The market is growing for the GPCR target class. The general adoption of cell-based assays continues to increase, so the division-arrest technology which facilitates that for our customers is also a growing market,” he said.
According to Singer, the calcium indicators and the acquired Sentigen technology are “very synergistic in that they all work together to provide a total solution to a drug discovery partner.
“A drug discovery partner might be interested first in a primary screen and looking at a calcium response, and that’s what the Fluo 3 and Fluo 4 are used for,” said Singer. “It’s the most pervasive assay in all of biology, because calcium changes are indicative of many, many different cellular events. The protein-protein interaction assays that Sentigen brings us will be used for a subset of drug candidates, but many of those may have been screened first for calcium.”
Singer said that although the company’s recent focus in acquiring technologies and businesses has centered on cell analysis technologies, “that does not mean we’re not still focused on protein analysis.
“You may see us acquire more technologies, companies, other things in that area,” she said. “But there is a greater focus on cell-based assays — that is simply because those cell-based assays move us closer to putting biology into context, rather than looking at molecules in isolation. As we build the toolbox, we’re going to be moving more and more to understand the cell, the cell in its milieu, and how it interacts — and that is a very deliberate, broad strategy.”

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