While screening hybridomas last year for monoclonalantibodies against gonorrhea, investigators at the Centers forDisease Control (CDC) in Atlanta found some antibodies thatlooked promising but turned out to be duds. "So we went backand looked at the hybridoma supernatant and found that allthe bactericidal activity against Neisseria gonorrhoeae was dueto a novel, low-molecular-weight peptide produced by B cells,"said Stephen Morse, head of laboratory research at the CDC'sdivision of sexually transmitted diseases.
Last month CDC filed for a U.S. patent on the peptide, describedin its application (No. 08/070,151) as "Antibacterial Compoundand Related Methods." On Monday the National Institutes ofHealth's Office of Technology Transfer (OTT) submitted themicrobe-killing peptide to the Federal Register as agovernment-owned invention, available for licensing andcommercialization. The notice is expected to run this week, saidMark Hankins, OTT's licensing specialist for the peptide.
Meanwhile, Morse told BioWorld, two unnamed biotechnologyR&D companies have already signed confidentiality agreementsto examine the patent application, with a view towardlicensing.
According to Morse, "This particular patent-pending peptide isdifferent from other, previously described, so-called 'defensin'-like molecules produced by leukocytes and other types ofphagocytic cells."
His group at CDC has purified the 11-amino acid, 1,500-kDpeptide by HPLC and characterized it by mass spectrometry."It's capable of killing a wide range of microorganisms, all theway from Gram negative to Gram positive to mycobacteria."Right now it's being produced by a B-cell hybridoma, whichalso generates a monoclonal antibody, "but the antibody hasnothing to do with our compound."
For a hybridoma to manufacture peptides directly is alsosomething new, Morse observed. With no clue as to its genesequence, he hasn't tried to synthesize the peptide yet, butexpects prospective licensees to do that either independentlyor jointly with CDC by a cooperative research and developmentagreement (CRADA). This would presumably also elucidate thecompound's mode of action, which so far remains unknown.
An in vivo study in mice demonstrated the peptide's infection-fighting capability. Fifteen rodents got the drug bysubcutaneous injection four hours after being inoculated withlethal Group B Streptococcus pyogenes. Another 15 receivedplacebo saline shots. These controls all died, while 13 of the 15treated with the peptide survived.
In vitro, the still-unnamed compound has killed such humanand animal pathogens as Neisseria gonorrhoeae, Gardnerellavaginalis, Staphylococcus aureus, Mobiluncus species, Moraxellabovis and Streptococcus equi.
Topical spraying and subcutaneous injection, the patent claims,are two preferred modes of administering the compound,notably for sexually transmitted diseases. It can also killmicroorganisms found in milk-producing animals without theside effects of antibiotics.
Lead inventor on the patent application is Edwin Ades, chief ofthe biological products branch in CDC's Scientific ResourcesProgram. Among Ades' other inventions is the patent-pending"Immortilization of Endothelial Cell Line," applied for in April1991 (application No. 07/679,674). It has also been filed for inEurope, said Elaine Ray, OTT licensing coordinator, who alsosubmitted it on Monday to run in the Federal Register. "Sandozand one or two other companies are evaluating Ades'endothelial cell lines" for possible licensure, said CDC's tech-transfer officer, R. Eric Greene.
For more information, contact Ray at (301) 496-7735.
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.