Isis Pharmaceuticals said Tuesday that it was issued a U.S.patent covering a new class of chemical alterations that itbelieves could enhance the performance of antisensecompounds.

The patent covers antisense oligonucleotides with variouschemical polyamines attached. Polyamines could improve theeffectiveness of oligonucleotides, which are designed toselectively bind to messenger RNA and, as a result, block acell's production of disease-causing proteins.

The addition of polyamines is "just one piece of theoligonucleotide-modification strategy we've taken from thebeginning," said Christopher Mirabelli, Isis' senior vicepresident. It is, however, the first to be issued a patent, U.S.patent 5,138,045.

Mirabelli declined to give details of other oligonucleotidemodifications that are in development at Isis. But the workincludes changes to the chemical bases and sugars ofoligonucleotides, all aimed at improving their pharmacologicalproperties, he said.

"One patent on its own is important, but what's reallysignificant is the combination" of several oligonucleotidemodifications, Mirabelli said. Making several modifications tofine-tune an oligonucleotide's performance will likely be thebasis for the coming second-generation antisense compounds,he said.

Isis (NASDAQ:ISIP) of Carlsbad, Calif., has filed about 50 U.S.patent applications, and fully half of them cover methods foraltering oligonucleotides, Mirabelli said.

As for polyamines, "in terms of their eventual importance (inantisense), that's not clear," he said. But selected polyaminescould help antisense development on two fronts. They mightincrease an oligonucleotides' binding affinity to the cell'smessenger RNA, and they may possess specific properties toenhance an oligonucleotide's ability to penetrate a cell wall orprolong its effectiveness in the body. Their potential shouldbecome clearer over the next 12 to 24 months, as Isisresearchers continue to study their actions, Mirabelli said.

Polyamines are not likely to play a role in Isis' initial antisenseproducts, such as a therapeutic for treating humanpapillomavirus, the first antisense compound to enter U.S.clinical trials, or several anti-viral therapeutics that are nownearing clinical trials, Mirabelli said.

-- Ray Potter Senior Editor

(c) 1997 American Health Consultants. All rights reserved.

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