St. Louis, April 13, 1999 -- After waiting for nearly 18 years, Roy Curtiss III, Ph.D., George William and Irene Koechig Freiberg Professor of Biology at Washington University in St. Louis, was granted a United States patent for his genetically engineered bacterial antigen delivery system March 30, 1999.
The patent, "Recombinant Avirulent Bacterial Antigen Delivery System," is number 5, 888, 799. It was originally filed on October 22, 1981. Washington University and the University of Alabama, Birmingham (UAB) will share patent income equally from any vaccine marketed to combat any bacterial, viral, fungal or parasitic disease using Curtiss' concept.
Curtiss developed the system while on the faculty of UAB in the late 1970s and early 1980s and at Washington University since 1983. The patent covers composition, manufacture and use of live attenuated, or weakened, derivatives of disease-causing bacteria genetically engineered to express foreign antigens, or proteins, in a vaccine; the vaccine then homes in on lymph tissue in an individual to induce immune responses against the foreign antigens.
Curtiss conceived the initial ideas for the patent in the late 1970s and early 1980s when he was using gene cloning to express protein antigens from streptococcal bacteria in E. coli. One purpose of these studies was to develop a recombinant vaccine that would induce anti-streptococcal immunity in an individual after taking an oral vaccine.
In 1981, when Curtiss filed the patent application, introducing genes from one pathogen into another was not possible because such gene cloning was prohibited by the National Institutes of Health (NIH) Guidelines for Recombinant DNA Research. Curtiss helped draft the guidelines in the 1970s as an original member of the NIH Recombinant DNA Advisory Committee. Although international patents on this technology first were granted in 1989, the U.S. Patent and Trademark Office had ruled in 1984 that the invention was not far enough advanced to be patentable.
However, in 1984, when it became possible to introduce genes from one pathogen into attenuated strains of another pathogen, Curtiss began to introduce streptococcal genes into attenuated types of Salmonella typhimurium. This led to his filing a Continuation-In-Part application on Sept. 9, 1985, which ultimately served as the basis for the patent issued this year.
According to Curtiss, securing the patent required that he demonstrate to the patent examiner a number of different advantages in using Salmonella: the ability to express a diversity of antigen genes from various bacteria, viruses, parasites and fungi in Salmonella; and the importance of the secretory immunoglobin (IgA) response. The IgA response occurs in such secretions as breast milk, tears and saliva and other areas where bacteria and viruses can enter the body. Curtiss's system invokes IgA immunity as a first line of defense against infection. At the time of patent application filing, there was almost no information about mucosal immunity in standard textbooks on immunology.
The technology currently is being used to develop recombinant vaccines to prevent or therapeutically treat infections due to Heliobacter pylori, which causes ulcers, Campylobacter jejuni, which causes diarrhea in poultry and humans, Mycobacterium tuberculosis, hepatitis B virus and a number of other pathogens for agricultural animals.
The patent has been licensed to MEGAN Health, Inc., a biotechnology company in St. Louis that is commercializing much of the technology that has arisen from research in Curtiss' laboratory over the past 20 years. Curtiss has a financial interest in MEGAN Health.
Two vaccines using Curtiss approaches to attenuate bacteria have been approved by the United States Department of Agriculture and are being marketed for use in preventing Salmonella infections in poultry and swine. Legal aspects of the patent have been handled over the past ten years by Ann Pokalsky and Frank Di Giglio, of Scully, Scott, Presser and Murphy of Garden City, New York.