Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
1999-11-19
2003-03-18
Barts, Samuel (Department: 1623)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C536S123130, C514S054000, C514S053000, C514S023000, C514S075000, C424S195110
Reexamination Certificate
active
06534648
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to the isolation and use of lipopolysaccharides from eukaryotic algae. More particularly, the present invention relates to the isolation of algal lipopolysaccharides and their use to inhibit the release of TNF-alpha from macrophages and, thus, inhibit endotoxin-initiated sepsis or septic shock.
Lipopolysaccharides are high molecular weight amphipathic molecules typically associated with the cell walls of gram negative enteric bacteria. The lipopolysaccharides of gram negative bacteria are known as endotoxins and have been found to be responsible for the pathogenicity of the bacteria. The primary pathogenicity of gram negative bacteria is its physiological interaction with a host to initiate sepsis or septic shock.
When a gram negative bacterium enters a host it begins to reproduce. As the bacteria reproduces, a number of the lipopolysaccharide molecules from the cell walls of the bacteria are shed from the organisms and are released into the circulatory system of the host. The discarded lipopolysaccharide molecules then interact with the host's immune system and begin a cascade of immunorelated physiological reactions. The lipopolysaccharides interact with the host macrophages. The interaction of lipopolysaccharides with the macrophages stimulates these white cells to release the cellular hormone TNF-alpha (“TNF-a”). This TNF-a hormone negatively impacts the host and produces a series of stereotypical responses including elevated temperature, blood coagulation, changes in white blood cell morphology and increased activity of the immune response. These responses become increasingly severe and ultimately manifest clinically as sepsis or septic shock.
In the United States alone there are believed to be approximately 300,000 cases of sepsis annually. About 150,000 of these cases are fatal. Infants, the elderly and the immunocompromised, such as AIDS victims, cancer patients and transplant recipients, are particularly susceptible to sepsis. There are presently no satisfactory treatments or cures for endotoxin-initiated sepsis. Because endotoxins provoke immunological dysfunction, they cannot be used directly as immunization agents. There are currently no attenuated endotoxins or endotoxin counterparts that can be used as vaccines. The prevailing medical treatment for sepsis is founded on a symptomatic approach, treating the physical discomfort associated with the illness while hoping the disease is ultimately cured by the host's immune system. Unfortunately, as the medical field currently stands, the unlucky individual who has contracted sepsis must confront the real likelihood of death.
SUMMARY OF THE INVENTION
It is therefore a primary object of the present invention to provide a method and product for the inhibition of endotoxin-related sepsis or septic shock.
More particularly, it is an object of the present invention to provide a composition and method of using the composition to inhibit the release of TNF-a from macrophages in a host that has contacted enteric lipopolysaccharides from gram negative bacteria and, thereby, inhibit sepsis.
It is a further object of the present invention to describe a method for the isolation of a compound that can be used to inhibit the release of TNF-a from macrophages in a host that has contacted lipopolysaccharides from gram negative bacteria and, thereby, inhibit sepsis.
It is a more specific object of the present invention to disclose the isolation and purification of lipopolysaccharides from eukaryotic algae which, when introduced into a host, inhibit the release of TNF-a and, thereby, inhibit the initiation and escalation of endotoxin-initiated sepsis.
To accomplish these and other related objects, the present invention relates to the isolation and purification of lipopolysaccharides from several related strains of eukaryotic algae. These lipopolysaccharides have been shown to be structurally and functionally similar to the lipopolysaccharides of gram negative bacteria. The present invention also relates to the use of these algal lipopolysaccharides to inhibit the release of TNF-a from macrophages, which has been linked with the initiation and escalation of sepsis as a result of bacterial endotoxins.
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Morrison David C.
Pardy R. L.
Royce Clare L.
Shnyra Alex
Barts Samuel
Board of Regents of the University of Nebraska
Khare Devesh
Shook Hardy & Bacon L.L.P.
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