Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Amino acid sequence disclosed in whole or in part; or...
Reexamination Certificate
1999-07-26
2001-05-08
Navarro, Albert (Department: 1645)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Amino acid sequence disclosed in whole or in part; or...
C424S192100, C424S193100, C424S197110, C424S234100, C424S263100, C530S350000
Reexamination Certificate
active
06228364
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to newly identified polynucleotides and polypeptides, and their production and uses, as well as their variants, agonists and antagonists, and their uses. In particular, in these and in other regards, the invention relates to novel polynucleotides and polypeptides of the gidA family, hereinafter referred to as “gidA1”.
BACKGROUND OF THE INVENTION
Chlamydiaceae is a family of obligate intracellular parasites. All members share a common developmental cycle. Chlamydia infect a wide range of vertebrate host, particularly humans.
Chlamydia trachomitis
is one of the two recognized species of Chlamydia. Human infections caused by
Chlamydia trachomitis
are widespread. This species is one of the most common cause of sexually transmitted disease in the world. It is also one of the main causes of infertility in humans.
The frequency of
Chlamydia trachomatis
infections has risen dramatically in the past 20 years. This has been attributed to the emergence of multiply antibiotic resistant strains and an increasing population of people with weakened immune systems. It is no longer uncommon to isolate
Chlamydia trachomatis
strains which are resistant to some or all of the standard antibiotics. This has created a demand for both new anti-microbial agents and diagnostic tests for this organism.
The first described gidA gene was that of
E. coli
(von Meyenburg et al (1980) ICN-UCLA Symp. Mol. Cell. Biol. 19, 137-159; Swissprot accession number P17112). The closest homolog of the
Chlamydia trachomitis
gidA1 polypeptide is
Pseudomonas putida
gidA (Ogasawara, N. & Yoshikawa, H. (1992) Mol. Microbiol. 6(5), 629-634; Swissprot accession number P25756). The closest homolog of the
Chlamydia trachomitis
gidA1 polynucleotide is
Borrelia burgdorferi
gidA (Old, I.G. et al. (1992) FEMS Microbiol. Lett. 99, 245-250; Genbank accession number Z12160).
Clearly, there is a need for factors, such as the novel compounds of the invention, that have a present benefit of being useful to screen compounds for antibiotic activity. Such factors are also useful to determine their role in pathogenesis of infection, dysfunction and disease. There is also a need for identification and characterization of such factors and their antagonists and agonists which can play a role in preventing, ameliorating or correcting infections, dysfunctions or diseases.
The polypeptides of the invention have amino acid sequence homology to a known Pseudomonas putida gidA protein.
SUMMARY OF THE INVENTION
It is an object of the invention to provide polypeptides that have been identified as novel gidA1 polypeptides by homology between the amino acid sequence set out in Table 1 [SEQ ID NO:2] and a known amino acid sequence or sequences of other proteins such as Pseudomonas putida gidA protein.
It is a further object of the invention to provide polynucleotides that encode. gidA1 polypeptides, particularly polynucleotides that encode the polypeptide herein. designated gidA1.
In a particularly preferred embodiment.,of the invention the polynucleotide compnses a region encoding gidA1 polypeptides comprising the sequence set out in Table 1 [SEQ ID NO:1] which includes a full length gene, or a variant thereof.
In another particularly preferred embodiment. of the invention there is a novel gidA1 protein from
Chlamydia trachomatis
comprising the amino acid sequence of Table 1 [SEQ ID NO:2], or a variant thereof.
In accordance with another aspect of the invention there is provided an isolated nucleic acid molecule encoding a mature polypeptide expressible by the
Chlamydia trachomatis
D/UW-3/CX strain.
As a further aspect of the invention, there are provided isolated nucleic acid molecules encoding gidA1, particularly
Chlamydia trachomatis
gidA1, including mRNAs, cDNAs, genomic DNAs. Further embodiments of the invention include biologically, diagnostically, prophylactically, clinically or therapeutically useful variants thereof, and compositions comprising the same.
In accordance with another aspect of the invention, there is provided the use of a polynucleotide of the invention for therapeutic or prophylactic purposes, in particular genetic immunization. Among the particularly preferred embodiments of the invention are naturally occurring allelic variants of gidA I and polypeptides encoded thereby.
Another aspect of the invention there are provided novel polypeptides of
Chlamydia trachomatis
referred to herein as gidA1 as well as biologically, diagnostically, prophylactically, clinically or therapeutically useful variants thereof, and compositions comprising the same.
Among the particularly preferred embodiments of the invention are variants of gidA1 polypeptide encoded by naturally occurring alleles of the gidA1 gene.
In a preferred embodiment of the invention there are provided methods for producing the aforementioned gidA1 polypeptides.
In accordance with yet another aspect of the invention, there are provided inhibitors to such polypeptides, useful as antibacterial agents, including, for example, antibodies.
In accordance with certain preferred embodiments of the invention, there are provided products, compositions and methods for assessing gidA1 expression, treating disease, for example, classic ocular trachora, inclusion conjunctivitis, genital trachoma, infant pneumonitis, Lymphogranuloma Venerium, incipient trachoma, keratitis, papillary hypertrophy, corneal infiltration, vulvovaginitis, ear infection, mucopurulent rhinitis, salpingitis, cervicitis, cervical follicles, prostatitis, proctitis, urethritis, lymphogranule inguinale, climatic bubo, tropical bubo, and esthiomene., assaying genetic variation, and administering a gidA1 polypeptide or polynucleotide to an organism to raise an immunological response against a bacteria, especially a
Chlamydia trachomatis
bacteria.
In accordance with certain preferred embodiments of this and other aspects of the invention there are provided polynucleotides that hybridize to gidA1 polynucleotide sequences, particularly under stringent conditions.
In certain preferred embodiments of the invention there are provided antibodies against gidA1 polypeptides.
In other embodiments of the invention there are provided methods for identifying compounds which bind to or otherwise interact with and inhibit or activate an activity of a polypeptide or polynucleotide of the invention comprising: contacting a polypeptide or polynucleotide of the invention with a compound to be screened under conditions to permit binding to or other interaction between the compound and the polypeptide or polynucleotide to assess the binding to or other interaction with the compound, such binding or interaction being associated with a second component capable of providing a detectable signal in response to the binding or interaction of the polypeptide or polynucleotide with the compound; and determining whether the compound binds to or otherwise interacts with and activates or inhibits an activity of the polypeptide or polynucleotide by detecting the presence or absence of a signal generated from the binding or interaction of the compound with the polypeptide or polynucleotide.
In accordance with yet another aspect of the invention, there are provided gidA1 agonists and antagonists, preferably bacteriostatic or bacteriocidal agonists and antagonists.
In a further aspect of the invention there are provided compositions comprising a gidA1 polynucleotide or a gidA1 polypeptide for administration to a cell or to a multicellular organism.
Various changes and modifications within the spirit and scope of the disclosed invention will become readily apparent to those skilled in the art from reading the following descriptions and from reading the other parts of the present disclosure.
GLOSSARY
The following definitions are provided to facilitate understanding of certain terms used frequently herein.
“Host cell” is a cell which has been transformed or transfected, or is capable of transformation or transfection by an exogenous polynucleotide sequence.
“Id
Kallender Howard
Reichard Raymond W.
Deibert Thomas S.
Gimmi Edward R.
King William T.
Navarro Albert
SmithKline Beecham Corporation
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