Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Recombinant or stably-transformed bacterium encoding one or...
Reexamination Certificate
2001-02-09
2003-07-01
Devi, S. (Department: 1645)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Recombinant or stably-transformed bacterium encoding one or...
C424S093200, C424S184100, C424S234100, C435S252300, C435S252100
Reexamination Certificate
active
06585977
ABSTRACT:
BACKGROUND
Periodontitis is an inflammatory disease of the tissues surrounding the teeth characterized by loss of the periodontal ligament attachment and alveolar bone support of the tooth. Periodontitis affects more than 49 million people in the United States and hundreds of millions of people worldwide and has been reported as a risk factor for cardiovascular disease and pre-term delivery of low-birth-weight infants. The most common cause of periodontitis is chronic Gram-negative bacterial infections. Among the Gram-negative bacteria implicated as a cause of periodontitis,
Porphyromonas gingivalis
is the major component of the flora in over 90% of adult periodontitis lesions.
Besides being a major etiological agent in adult human periodontitis,
Porphyromonas gingivalis
also causes aspiration pneumonia and necrotizing pneumonia, abscesses in brain, genitourinary tract and lung, as well as mediastinitis. By contrast,
P. gingivalis
is not normally found at healthy sites nor is it found in patients with gingivitis but with no accompanying periodontitis.
The current therapy for periodontitis is directed toward identifying, removing and controlling the etiologic factors, and then correcting the defects these pathogens have caused. These therapies include scaling and root planing, chemotherapy, periodontal surgery and periodic maintenance therapy. However, these treatments are not entirely effective because, for example, the pathogens can become resistant to chemotherapeutic agents.
Several potential virulence factors have been identified which appear to relate to the pathogenicity of
P. gingivalis
in periodontitis. These factors include fimbriae (adhesins), capsule (antiphagocytosis), lipopolysaccharide (bone resorption), proteases (specific and generalized tissue destruction) and a variety of toxic by-products (e.g., ammonia). Some of these factors have been purified and biochemically characterized. However, the specific roles, interactions, relative importance and regulation of these factors remains to be determined.
Therefore, there remains a need for effective prevention and treatment for periodontitis. Further, there remains a need for a modified strain of
P. gingivalis
that can be used as a host genetic background to determine the specific roles. interactions, relative importance and regulation of the potential virulence factors produced by wild-type
P. gingivalis.
SUMMARY OF THE INVENTION
According to one embodiment of the present invention, there is provided a non-virulent, recA defective mutant of
Porphyromonas gingivalis
. According to another embodiment of the present invention, there is provided a
Porphyromonas gingivalis
strain which is deposited at ATCC under accession number 202109.
According to another embodiment of the present invention, there is provided a pharmaceutical preparation comprising a mutant of
Porphyromonas gingivalis
according to the present invention.
According to another embodiment of the present invention, there is provided a method of decreasing the growth rate or reproduction rate of
Porphyromonas gingivalis
in a mammal, such as a human. The method comprises the step of administering to the mammal at least one dose of a non-virulent, recA defective mutant of
Porphyromonas gingivalis
, such as at least one dose of a
Porphyromonas gingivalis
strain which is deposited at ATCC under accession number 202109.
According to another embodiment of the present invention, there is provided a method of preventing or treating a
Porphyromonas gingivalis
infection such as periodontitis in a mammal, such as a human. The method comprises the step of administering to the mammal at least one dose of
Porphyromonas gingivalis
according to the present invention.
The methods of the present invention can be performed by administering to the mutant with the at least one dose of a non-virulent, recA defective mutant of
Porphyromonas gingivalis
via a route selected from the group consisting of a subcutaneous route, an intravenous route and an intramuscular route, among other routes. In a preferred embodiment, the methods of the present invention include administering at least one dose of a non-virulent, recA defective mutant of
Porphyromonas gingivalis
, wherein the dose is between about a 1×10
3
and 1×10
7
bacteria per kg of body weight of the mammal. More preferably, the dose is between about 1×10
5
and 1×10
6
bacteria per kg of body weight of the mammal.
REFERENCES:
patent: 6254863 (2001-07-01), Fletcher
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Aduse-Opoku, Joseph et al., “Character
Devi S.
Farah David A.
Loma Linda University
Sheldon & Mak PC
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