A low-tech route using nitric oxide blockers to treat sepsis hasbeen patented by U.S. researchers who are filing to get theircompounds into the clinic.

The nitric oxide route to stopping sepsis has been discussed inrecent editions of The Lancet, in some cases involving dramaticuses of common chemicals to reverse septic shock in patientsnear death.

Some researchers have assumed that the readily availablecompounds were not patentable, and therefore unlikelycandidates for commercial development.

But Robert Kilbourn, an oncologist at M.D. Anderson CancerCenter in Houston, on Wednesday told BioWorld that theCenter, the University of Texas and Cornell Medical College inNew York jointly hold an issued U.S. patent on a method ofusing arginine derivatives in nitric oxide-related shock.

"In 1989 I reported animal experiments showing nitric oxide isthe major mediator of septic shock," Kilbourn said. The patenton arginine-derived drugs that block nitric oxide, No.5,028,627, issued on July 2, 1991.

Analogs of the amino acid l-arginine block the arginine-inducedproduction of nitric oxide (NO), which dilates blood vessels. Inseptic shock, NO may cause blood pressure to fall and organs tofail.

Although existing NO inhibitors are easily obtained throughchemical supply houses, a use patent can make theircommercial development feasible.

The patent raises new issues for British scientists at Burroughs-Wellcome Laboratories in Kent, who have been testing arginineanalogs. "Whether the new agents that emerge from our labsand others will fall within the scope of patent remains to beseen," said Laurence Jenkins, deputy head of the patent groupat Wellcome. Novel chemicals that are not necessarily arginineanalogs might be found to work in sepsis, Jenkins said.

Use patents "are something of a novelty in Europe," he added.Jenkins said he was not sure whether Wellcome had yet filedfor any patents on nitric oxide inhibitors.

Meanwhile, Kilbourn and colleagues are filing to begin Phase Itrials of methylarginine to block the fall in blood pressurecaused by interleukin-2 when the cytokine is used to treatkidney cancer.

Although septic shock is not yet a focus, when a safe dose isdetermined in kidney cancer, Phase II trials of methylargininewill be designed for sepsis, kidney cancer and several otherconditions, Kilbourn said.

-- Roberta Friedman, Ph.D. Special to BioWorld

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