Isis Pharmaceuticals Inc. entered into a target validation collaboration with Merck & Co. Inc. to support Merck’s internal research and discovery efforts, the third collaboration between the two companies.

Isis, of Carlsbad, Calif., said its GeneTrove division will provide Merck with antisense-based tools to discover the biological role of genes selected by Merck before validating them as potential drug targets.

Specific terms of the deal were not disclosed.

“Merck is a strategic partner for Isis,” said Frank Bennett, vice president of antisense research at Isis. “We have a four-year history with them, first with HCV, and this further extends the relationship.”

In 1998, Isis and Merck, of Whitehouse Station, N.J., entered into a drug discovery partnership in hepatitis C that was expected to mean up to $50 million for Isis. Chemists from both companies were to design, synthesize and evaluate small molecules, which Merck would screen in enzymatic assays to identify hepatitis C replication inhibitors. Merck has the right to commercialize any drugs resulting from the collaboration, while Isis retains any technology for its antisense program. (See BioWorld Today, June 10, 1998.)

In May, Merck agreed to pay Isis up to $50 million in licensing and milestone fees for Isis’ preclinical Type II diabetes antisense drug candidate, ISIS 113715, which is still in the preclinical phase. That candidate was developed using Isis’ antisense technology. (See BioWorld Today, May 24, 2001.)

Bennett could not disclose how much Isis has received to date from Merck in any of its collaborations, but he did say that Isis has “achieved certain milestones” from licensing its Type II diabetes candidate to Merck. He said this latest agreement allows Merck to adopt Isis’ antisense technology more broadly.

“The value it brings to the pharmaceutical companies [is that] it helps them make decisions and avoid making very expensive investments in [misguided] drug discovery programs,” Bennett said.

Bennett described the antisense technology by explaining that antisense oligonucleotides are short synthetic nucleic acid compounds that bind to the RNA that codes for a protein of interest, which makes it inhibit the expression of a specific gene product. He said the technology is broadly applicable so that Isis can inhibit any gene in the human genome using this technology. The GeneTrove division can determine the consequences of inhibiting a gene, and then exploit that information for target validation.

Separately, Isis said the change of its stock symbol on Nasdaq from “ISIP” to “ISIS” went into effect. The move is designed to align its identity among investors with the company’s name. Isis’ stock fell 77 cents Thursday to close at $16.90.