Xoma Corp. reported this week that it may develop itsrecombinant human bactericidal/permeability increasingprotein (rBPI), Neuprex, for an expanded range of clinicalindications following a study on the agent published in lastweek's issue of the Journal of Biological Chemistry.
In identifying the functional domains of rBPI, a group ofresearchers led by Xoma scientist Roger Little found that rBPIbinds to heparin in vitro.
The finding may encourage Xoma (NASDAQ:XOMA) of Berkeley,Calif., to look at the agent for a new range of indications, acompany representative said. Little told BioWorld that theability of rBPI to inhibit the activity of heparin could lead toseveral therapeutic applications. The agent could potentially beused in post-surgical applications, in which it could neutralizethe effects of heparin used to inhibit blood clotting duringsurgery, he said.
Naturally occurring heparin also plays a role in angiogenesis(the formation of new blood vessels), said Little. Generally,angiogenesis only occurs in healthy adult females duringmenstruation and should not normally occur in adult males. Butit can take place in patients with cancer or other inflammatoryor autoimmune diseases, Little said. For example, it can indicatethe formation of vessels to supply blood flow to cancer tumors.An agent that could neutralize the body's natural heparin couldinhibit this process and be a valuable therapeutic.
Little observed, however, that other agents known to bind withheparin are also being evaluated for their therapeutic potential.Glycomed Inc. and Chiron Corp. are currently studying thebinding effects of heparin and basic fibroblast growth factor(bFGF). Repligen Corp. is developing platelet factor 4 for thepost-surgical neutralization of heparin. Protamine is the onlydrug currently on the market that is known to bind to heparin,but Little remarked that the salmon sperm derivative canproduce adverse reactions in some patients because it is a non-mammalian-derived protein.
In identifying the functional domains of rBPI, Little and hiscolleagues also were able to find a peptide that exhibitedactivity against Gram-positive bacteria, a Xoma representativesaid. The company has completed several Phase I studies ofrBPI as an anti-infective for Gram-negative infections, but mayuse the new findings to identify new drug candidates for Gram-positive infection.
Neuprex is based on natural human bactericidal/permeabilityincreasing protein found in certain white blood cells. Xomaholds an exclusive license to the patent covering the DNAsequences coding for human BPI and its fragments and for themanufacture of BPI-based proteins using recombinant DNAtechnology. BPI was discovered by Peter Elsbach and JerroldWeiss of the New York University Medical Center.
Xoma said it intends to present the first of its Phase I data onNeuprex against Gram-negative infection in March.
-- Karl A. Thiel Associate Editor
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