Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Reexamination Certificate
1997-12-18
2001-10-09
Kunz, Gary L. (Department: 1647)
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
C435S320100, C435S252300, C536S023700, C536S023100
Reexamination Certificate
active
06300094
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, the invention relates to novel polynucleotides and polypeptides of the ABC transporter family, hereinafter referred to as “Novel ABC transporter”.
BACKGROUND OF THE INVENTION
It is particularly preferred to employ Staphylococcal genes and gene products as targets for the development of antibiotics. The Staphylococci make up a medically important genera of microbes. They are known to produce two types of disease, invasive and toxigenic. Invasive infections are characterized generally by abscess formation effecting both skin surfaces and deep tissues. Staphylococcus aureus is the second leading cause of bacteremia in cancer patients. Osteomyelitis, septic arthritis, septic thrombophlebitis and acute bacterial endocarditis are also relatively common. There are at least three clinical conditions resulting from the toxigenic properties of Staphylococci. The manifestation of these diseases result from the actions of exotoxins as opposed to tissue invasion and bacteremia. These conditions include: Staphylococcal food poisoning, scalded skin syndrome and toxic shock syndrome.
The frequency of
Staplhylococcus aureus
infections has risen dramatically in the past few decades. 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
Staphylococcus aureus
strains which are resistant to some or all of the standard antibiotics. This phenomenon has created a demand for both new anti-microbial agents, vaccines, and diagnostic tests for this organism.
Clearly, there exists a need for factors, such as the Novel ABC transporter embodiments 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 to find ways to prevent, ameliorate or correct such infection, dysfunction and disease.
Certain of the polypeptides of the invention possess amino acid sequence homology to a known
Archaeoglobus fulgidus
ABC transporter (AE001033) protein. (Higgins et al. 1990. J. Bioenerg. Biomembr 22:571-592; Aguilar_Bryan et al 1995 Science 268:423-426. Rosteck et al 1991 Gene 102:27-32; Accession numbers AE001023, C64488.)
SUMMARY OF THE INVENTION
It is an object of the invention to provide polypeptides that have been identified as novel Novel ABC transporter 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
Archaeoglobus fulgidus
ABC transporter (AE001033) protein.
It is a further object of the invention to provide polynucleotides that encode Novel ABC transporter polypeptides, particularly polynucleotides that encode the polypeptide herein designated Novel ABC transporter.
In a particularly preferred embodiment of the invention, the polynucleotide comprises a region encoding Novel ABC transporter polypeptides comprising a 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 Novel ABC transporter protein from
Staphylococcus aureus
comprising the amino acid sequence of Table 1 [SEQ ID NO:2], or a variant thereof
As a further aspect of the invention there are provided isolated nucleic acid molecules encoding Novel ABC transporter, particularly
Staphylococcis aureus
Novel ABC transporter, 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 Novel ABC transporter and polypeptides encoded thereby.
As another aspect of the invention, there are provided novel polypeptides of
Staphylococcus aureus
referred to herein as Novel ABC transporter 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 Novel ABC transporter polypeptide encoded by naturally occurring alleles of the Novel ABC transporter gene.
In a preferred embodiment of the invention, there are provided methods for producing the aforementioned Novel ABC transporter 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 Novel ABC transporter expression, treating disease, assaying genetic variation, and administering a Novel ABC transporter polypeptide or polynucleotide to an organism to raise an immunological response against a bacteria, especially a
Staphylococcus aureus
bacteria.
In accordance with certain preferred embodiments of this and other aspects of the invention, there are provided polynucleotides that hybridize to Novel ABC transporter polynucleotide sequences, particularly under stringent conditions.
In certain preferred embodiments of the invention, there are provided antibodies against Novel ABC transporter 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 Novel ABC transporter agonists and antagonists, preferably bacteriostatic or bacteriocidal agonists and antagonists.
In a further aspect of the invention, there are provided compositions comprising a Novel ABC transporter polynucleotide or a Novel ABC transporter 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.
DESCRIPTION OF THE INVENTION
The invention relates to novel Novel ABC transporter polypeptides and polynucleotides as described in greater detail below. In particular, the invention relates to polypeptides and polynucleotides of a novel Novel ABC transporter of
Staphylococcus aureus
, which is related by amino acid sequence homology to
Archaeoglobus fulgidus
ABC transporter (AE001033) polypeptide. The invention relat
Traini Christopher Michael
Warren Richard Lloyd
Deibert Thomas S.
Gimmi Edward R.
Hayes Robert C.
King William T.
Kunz Gary L.
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