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ISIS 113715

Ionis Pharmaceuticals, Inc.

Drug Names(s): ISIS 113715

Description: ISIS 113715 is an antisense inhibitor of the gene encoding PTP-1B, a negative regulator of insulin receptor signaling.

Binding of insulin to the receptor on the plasma membrane results in autophosphorylation, and the activated insulin receptor then begins to phosphorylate its various substrates to initiate the insulin signaling cascade. At the same time, it undergoes internalization into endosomes (a compartment of the membrane transport pathway from the plasma membrane to the lysosome). Acidification of the endosome lumen causes insulin dissociation from the receptor, which prevents further activation, and the receptor then undergoes dephosphorylation, at which time it is then sorted back to the plasma membrane. PTP-1b appears to be involved in the dephosphorylation. In preclinical studies, PTP-1b knockout mice (ie where the gene has been removed) have enhanced insulin sensitivity and resistance to diet-induced obesity.

Deal Structure: In May 2001, Isis licensed ISIS 113715 to Merck. Under the agreement, Merck has the right to undertake the development and commercialization of ISIS 113715 in exchange for an upfront fee and milestone payments and royalties to Isis upon its successful development and approval. In December 2003, Isis Pharmaceuticals reacquired full product rights to ISIS 113715 from Merck.

Partners: Merck & Co., Inc.

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