Incyte Pharmaceuticals Inc. announced Tuesday that it hasreceived its second use patent on bacterial permeabilityincreasing (BPI) proteins for treating endotoxic shock. The U.S.patent, No 5,171,739, also covers genetically engineered BPIvariants and their prophylactic applications.

This extends the coverage the Palo Alto, Calif., company has onBPI. Last February it received a patent covering the use ofhuman BPI, or analogs (or fragments) of the protein, fortreating endotoxin-related disorders, as well as ways ofpurifying BPI. BPI, a protein made by neutrophils, is the body'snatural inactivator of bacterial endotoxin.

Genentech Inc. (NYSE:GNE), whose scientists originally clonedthe BPI protein in collaboration with researchers at New YorkUniversity (NYU), entered into a $14 million collaboration withIncyte in September 1991 to develop BPI. The NYU researcherswho discovered BPI are also collaborating with Xoma Corp.(NASDAQ:XOMA) on BPI. In 1990, NYU granted Xoma exclusiverights to BPI and fragments of BPI. Patent applications arepending in the U.S. and elsewhere on the Xoma-NYU molecules.

The intellectual property situation is not as complex as itseems, Randal Scott, Incyte's vice president of research anddevelopment, told BioWorld. Because BPI was first discoveredand reported on in 1978, it's been in the public domain forquite some time, and it's difficult to imagine that "anyone has aproprietary position on the molecule itself," Scott explained.

But for most of those years in the public eye, researchers knewonly about BPI's role as a potent antibiotic for gram-negativebacteria. Scott told BioWorld that it was Incyte scientists whodiscovered that BPI is a potent anti-endotoxin, as well.

"The newly issued patent strengthens Incyte's proprietaryposition on second-generation products," said Incyte PresidentRoy Whitfield. Nevertheless, the privately held company hasfiled additional patent applications on BPI "that would covernew composition of matter and DNA constructs," Scott toldBioWorld. "We'll wait and see if other patents issue elsewhere,"he added.

Incyte's partner, Genentech, is "in control of productdevelopment," Scott said, but several second-generation BPIproducts are already undergoing extensive preclinical tests inanimals. "We expect soon to be in a position to select the mostpromising for clinical development," said Whitfield.

Xoma also seems to be committed to developing BPI fortreating infections. In fact, in late October, when the Berkeley,Calif., company announced a major restructuring, BPI becameits new focus. "We've decided to shift Xoma's principal researchfocus to BPI because of its clinical and commercial potential,"Xoma President Jack Costello said at the time. Xomaspokeswoman Carol DeGuzman added, "In our animal modelsand lab testing, BPI has shown good results as an anti-bacterialand anti-endotoxin."

Xoma planned to file for FDA authorization to begin humantesting of a genetically engineered portion of BPI protein in thefirst quarter of 1993.

Various products based on tumor necrosis factor (TNF) or theinterleukins are being developed to counter sepsis. Thus, someindustry observers consider that Synergen Inc.'s(NASDAQ:SYGN) interleukin-1 receptor antagonist, Antril, willprove stiff competition to any BPI product for treating septicshock. But Incyte's Scott said, "We expect anti-endotoxins willwork in synergy with anti-cytokines."

-- Jennifer Van Brunt Senior Editor

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

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