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
1997-05-14
2002-02-19
Martinell, James (Department: 1632)
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, C536S023100, C536S023700
Reexamination Certificate
active
06348328
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to newly identified polynucleotides, polypeptides encoded by such polynucleotides, the uses of such polynucleotides and polypeptides, as well as the production of such polynucleotides and polypeptides and recombinant host cells transformed with the polynucleotides. This invention also relates to inhibiting the biosynthesis or action of such polynucleotides or polypeptides and to the use of such inhibitors in therapy. Preferred embodiments of the invention include Streptococcal polypeptides and polynucleotides, particularly those of
Streptococcus pneumoniae.
BACKGROUND OF THE INVENTION
The Streptococci make up a medically important genera of microbes known to cause several types of disease in humans, including otitis media, pneumonia and meningitis. Since its isolation more than 100 years ago,
Streptococcus pneumoniae
has been one of the more intensively studied microbes. For example, much of our early understanding that DNA is, in fact, the genetic material was predicated on the work of Griffith and of Avery, Macleod and McCarty using this microbe. Despite the vast amount of research with
S. pneumoniae
, many questions concerning the virulence of this microbe remain.
While certain Streptococcal factors associated with pathogenicity have been identified, e.g., capsule polysaccharides, peptidoglycans, pneumolysins, PspA Complement factor H binding component, autolysin, neuraminidase, peptide permeases, hydrogen peroxide, IgA1 protease, the list is certainly not complete. Further very little is known concerning the temporal expression of such genes during infection and disease progression in a mammalian host. Discovering the sets of genes the bacterium is likely to be expressing at the different stages of infection, particularly when an infection is established, provides critical information for the screening and characterization of novel antibacterials which can interrupt pathogenesis. In addition to providing a fuller understanding of known proteins, such an approach will identify previously unrecognised targets.
BRIEF DESCRIPTION OF THE INVENTION
This invention provides novel proteins, particularly those from
Streptococcus pneumoniae
, strain 0100993, characterised in that it comprises the amino acid sequences given herein or fragments, analogues or derivatives thereof.
In accordance with another aspect of the present invention, there are provided polynucleotides (DNA or RNA) which encode such polypeptides.
In particular the invention provides polynucleotides having the DNA sequences given herein.
The invention also relates to novel oligonucleotides derived from the sequences given herein which can act as PCR primers in the process herein described to determine whether or not the
Streptococcus pneumoniae
gene identified herein in whole or in part is expressed in infected tissue. It is recognised that such sequences will also have utility in diagnosis of the stage of infection and type of infection the pathogen has attained. The proteins so identified are also useful as targets in screens designed to identify antimicrobial compounds.
It is an object of the invention to provide polypeptides that have been identified as novel polypeptides by homology between the amino acid sequence set out in the Sequence Listing and a known amino acid sequence or sequences of other proteins such as the proteins identified under the heading Identity in Table 1.
It is a further object of the invention to provide polynucleotides that encode polypeptides set forth in the Sequence Listing, particularly polynucleotides that encode the polypeptide set forth in the Sequence Listing.
In a particularly preferred embodiment of the invention the polynucleotide comprises a region encoding polypeptides comprising the sequence set out in the Sequence Listing, or a variant thereof.
In another particularly preferred embodiment of the invention there is a novel protein from comprising an amino acid sequence of the Sequence Listing, or a variant thereof.
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 the polynucleotides set forth in the Sequence Listing and polypeptides encoded thereby.
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 expression of the sequences the Sequence Listing, treating disease, for example, otitis media, conjunctivitis, pneumonia, bacteremia, meningitis, sinusitis, pleural empyema and endocarditis, and most particularly meningitis, such as for example infection of cerebrospinal fluid, assaying genetic variation, and administering a polypeptide or polynucleotide of the invention to an organism to raise an immunological response against a bacteria, especially a
Streptococcus pneumoniae
bacteria
In accordance with certain preferred embodiments of this and other aspects of the invention there are provided polynucleotides that hybridize to polynucleotide sequences of the invention, particularly under stringent conditions.
In certain preferred embodiments of the invention there are provided antibodies against polypeptides of the invention.
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 detetable 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 polypetide 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 agonists and antagonists of the polynucleotide and/or polypeptides of the invention, preferably bacteriostatic or bacteriocidal agonists and antagonists.
In a further aspect of the invention there are provided compositions comprising a polynucleotide or a polypeptide of the invention 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 ring the other parts of the present disclosure.
DETAILED DESCRIPTION OF THE INVENTION
Each of the DNA sequences provided herein may be used in the discovery and development of antibacterial compounds. Because each of the sequences contains an open reading frame (ORF) with appropriate initiation and termination codons, the encoded protein upon expression can be used as a target for the screening of antimicrobial drugs. Additionally, the DNA sequences encoding preferably the amino terminal regions of the encoded protein or the Shine-Delgarno region can be used to construct antisense sequences to control the expression of the coding sequence of interest. Furthermore, many of the sequences disclosed herein also provide regions upstream and downstream from the encoding sequence. These sequences are useful as a source of regulatory elements for the control of bacterial gene expression. Such sequences are conveniently
Black Michael Terence
Hodgson John Edward
Knowles David Justin Charles
Nicholas Richard Oakley
Stodola Robert King
Deibert Thomas S.
Gimmi Edward R.
Martinell James
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