Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
1998-04-24
2001-08-14
Swartz, Rodney P (Department: 1645)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C435S252100, C435S253400, C435S320100, C514S04400A, C530S300000, C530S333000, C530S350000, C530S820000, C530S825000, C536S023100, C536S024300, C536S024320, C536S024330
Reexamination Certificate
active
06274719
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 polynucleotides and polypeptides of the glycopeptidase family, as well as their variants, hereinafter referred to as “gcp,” “gcp polynucleotide(s),” and “gcp polypeptide(s).”
BACKGROUND OF THE INVENTION
The Streptococci make up a medically important genera of microbes known to cause several types of disease in humans, including, 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. 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. It is particularly preferred to employ Streptococcal genes and gene products as targets for the development of antibiotics.
Several cell surface associated proteins of the Staphylococci and Streptococci involved in microbial adhesion to different host tissues and considered to be important factors in bacterial pathogenesis have been identified in the last decade (see Patti, J. M., et al., MSCRAMM-Mediated Adherence of Microorganisms to Host Tissues (1994) Annu. Rev. Microbiol. 48:85-617).
Different approaches have been put forward to address such proteins from
Staphylococcus aureus
as antibacterial targets, e.g. fibronectin binding proteins (EP0294349, EP0397633, WO94/18327), fibrinogen binding protein (WO94/06830), collagen binding protein (WO92/07002) and bone sialoprotein binding protein (WO94/13310). The binding proteins or binding fragments thereof are used as antibacterial agents to block binding of the organism to host tissue, as vaccines to raise antibodies to the organism in the host animal or as antigens to raise therapeutic antibodies which can be used to block binding of the organism to host tissue.
The frequency of
Streptococcus pneumoniae
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
Streptococcus pneumoniae
strains which are resistant to some or all of the standard antibiotics. This phenomenon has created an unmet medical need and demand for new anti-microbial agents, vaccines, drug screening methods, and diagnostic tests for this organism.
Moreover, the drug discovery process is currently undergoing a fundamental revolution as it embraces “functional genomics,” that is, high throughput genome- or gene-based biology. This approach is rapidly superseding earlier approaches based on “positional cloning” and other methods. Functional genomics relies heavily on the various tools of bioinformatics to identify gene sequences of potential interest from the many molecular biology databases now available as well as from other sources. There is a continuing and significant need to identify and characterize further genes and other polynucleotides sequences and their related polypeptides, as targets for drug discovery.
Clearly, there exists a need for polynucleotides and polypeptides, such as the gcp embodiments of the invention, that have a present benefit of, among other things, 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 significant amino acid sequence homology to a known
Pasteurella haemolytica
gcp protein, GenBank D88802, SwissProt P36175, Abdullah K M, Lo R Y C, Mellors A. J. Bacteriol. 173:5597-5603 (1991), Rawlings N D, Barrett A J. Meth. Enzymol. 248:183-228 (1995); PCT Publication WO98/06734, published Feb. 19, 1998; and PCT Publication WO97/37026, published 9 October 1997.
SUMMARY OF THE INVENTION
The present invention relates to gcp, in particular gcp polypeptides and gcp polynucleotides, recombinant materials and methods for their production. In another aspect, the invention relates to methods for using such polypeptides and polynucleotides, including the treatment of microbial diseases, amongst others. In a further aspect, the invention relates to methods for identifying agonists and antagonists using the materials provided by the invention, and for treating microbial infections and conditions associated with such infections with the identified compounds. In a still further aspect, the invention relates to diagnostic assays for detecting diseases associated with microbial infections and conditions associated with such infections, such as assays for detecting gcp expression or activity.
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 gcp polypeptides and polynucleotides as described in greater detail below. In particular, the invention relates to polypeptides and polynucleotides of a gcp of
Streptococcus pneumoniae
, which is related by amino acid sequence homology to
Pasteurella haemolytica
gcp polypeptide. The invention relates especially to gcp having the nucleotide and amino acid sequences set out in Table 1 as SEQ ID NO: 1 and SEQ ID NO: 2 respectively.
TABLE 1
gcp Polynucleotide and Polypeptide Sequences
(A)
Streptococcus pneumoniae
gcp polynucleotide sequence [SEQ ID NO:1].
5′-
ATGAAGGATAGATATATTTTAGCATTTGAGACATCCTGTGATGAGACCAGTGTCGCCGTCTTGAAAAACGAC
GATGAGCT
CTTGTCCAATGTCATTGCTAGTCAAATTGAGAGTCACAAACGTTTTGGTGGCGTAGTGCCCGAAGTAGCCAG
TCGTCACC
ATGTCGAGGTCATTACAGCCTGTATCGAGGAGGCATTGGCAGAAGCAGGGATTACCGAAGAGGACGTGACAG
CTGTTGCG
GTTACCTACGGACCAGGCTTGGTCGGAGCCTTGCTAGTTGGTTTGTCAGCCGCCAAGGCCTTTGCTTGGGCT
CACGGACT
TCCACTGATTCCTGTTAATCACATGGCTGGGCACCTCATGGCAGCTCAGAGTGTGGAGCCTTTGGAGTTTCC
CTTGCTAG
CCCTTTTAGTCAGTGGTGGGCACACAGAGTTGGTCTATGTTTCTGAGGCTGGCGATTACAAGATTGTTGGAG
AGACACGA
GACGATGCAGTTGGGGAGGCTTATGACAAGGTCGGTCGTGTCATGGGCTTGACCTATCCTGCAGGTCGTGAG
ATTGACGA
GCTGGCTCATCAGGGGCAGGATATTTATGATTTCCCTCGTGCTATGATTAAGGAAGATAATCTGGAGTTTTC
ATTCTCTG
GTTTGAAATCTGCCTTTATCAATCTTCACCACAATGCCGAGCAAAAGGGAGAAAGTCTGTCTACAGAGGATT
TGTGTGCT
TCCTTCCAAGCAGCTGTACTGGATATTCTCATGGCAAAAACCAAGAAGGCTTTGGAGAAATATCCTGTTAAA
ACCCTGGT
TGTGGCAGGTGGTGTGGCAGCCAATAAAGGTCTCAGAGAACGCCTAGCAGCCGAGGTTACAGATGTCAAGGT
CATCATTC
CACCTCTGCGCCTCTGCGGAGACAATGCAGGTATGATTGCTTATGCCAGTGTCAGCGAGTGGAACAAAGAAA
ACTTTGCA
AACTTGGACCTCAATGCCAAACCAAGCCTCGCTTTTGATACCATGGAATAA-3′
(B)
Streptococcus pneumoniae
gcp polypeptide sequence deduced from a
polynucleotide sequence in this table [SEQ ID NO:2].
NH
2
-
MKDRYILAFETSCDETSVAVLKNDDELLSNVIASQIESHKRFGGVVPEVASRHHVEVITACIEEALAEAGIT
EEDVTAVA
VTYGPGLVGALLVGLSAAKAFAWAHGLPLIPVNHMAGHLMAAQSVEPLEFPLLALLVSGGHTELVYVSEAGD
YKIVGETR
DDAVGEAYDKVGRVMGLTYPAGREIDELAHQGQDIYDFPRAMIKEDNLEFSFSGLKSAFINLHHNAEQKGES
LSTEDLCA
SFQAAVLDILMAKTKKALEKYPVKTLVVAGGVAANKGLRERLAAEVTDVKVIIPPLRLCGDNAGMIAYASVS
EWNKENFA
NLDLNAKPSLAFDTME-COOH
Deposited Materials
A deposit containing a
Streptococcus pneumoniae
0100993 strain has been deposited with the National Collections of Industrial and Marine Bacteria Ltd. (herein “NCIMB”), 23 St. Machar Drive, Aberdeen AB2 IRY, Scotland on Apr. 11, 1996 and assigned deposit number 40794. The deposit was descri
Biswas Sanjoy
Chalker Alison Frances
Holmes David
Ingraham Karen A
Palmer Leslie Marie
Deibert Thomas S.
Gimmi Edward R.
King William T.
SmithKline Beecham Corporation
Swartz Rodney P
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