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
1998-07-22
2001-03-06
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...
C424S190100, C424S192100, C424S234100, C424S244100, C530S350000
Reexamination Certificate
active
06197300
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 ftsZ family, as well as their variants, hereinafter referred to as “ftsZ,” “ftsZ polynucleotide(s),” and “ftsZ polypeptide(s)” as the case may be.
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
Streptococcus 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.
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 ftsZ embodiments of the invention, that have a present benefit of, among other things, being useful to screen compounds for antimicrobial 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.
SUMMARY OF THE INVENTION
The present invention relates to ftsZ, in particular ftsZ polypeptides and ftsZ polynucleotides, recombinant materials and methods for their production. In another aspect, the invention relates to methods for using such polypeptides and polynucleotides, including 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 agonist or antagonist 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 ftsZ 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 ftsZ polypeptides and polynucleotides as described in greater detail below. In particular, the invention relates to polypeptides and polynucleotides of a ftsZ of
Streptococcus pneumoniae,
which is related by amino acid sequence homology to ftsZ,
E. coli
polypeptide. (NCBI non-redundant protein sequence database entry gi|3287842|sp|08458|FTSZ_ENTHR, Cell division protein FtsZ,
Enterococcus hirae,
length 413 AA; TIGR microbial database,
Streptococcus pneumoniae
partial sequence, release 1, Nov. 21, 1997, contig 4118. The Institute for Genome Research, Rockville, Md.)) The invention relates especially to ftsZ having the nucleotide and amino acid sequences set out in Table 1 as SEQ ID NO:1 or 3 and SEQ ID NO:2 or 4 respectively. Note that sequences recited in the Sequence Listing below as “DNA” represent an exemplification of the invention, since those of ordinary skill will recognize that such sequences can be usefully employed in polynucleotides in general, including ribopolynucleotides.
TABLE 1
ftsZ Polynucleotide and Polypeptide Sequences
(A)
Streptococcus pneumoniae
ftsZ polynucleotide sequence [SEQ ID NO:1].
5′-
atgacattttcatttgatacagctgctgctcaaggggcagtgattaaagtaattggtgtcggtggaggtggtgg
caatgc
catcaaccgtatggtcgacgaaggtgttacaggcgtagaatttatcgcagcaaacacagatgtacaagcattga
gtagta
caaaagctgagactgttattcagttgggacctaaattgactcgtggtttgggtgcaggaggtcaacctgaggtt
ggtcgt
aaagccgctgaagaaagcgaagaaacactgacggaagctattagtggtgccgatatggtcttcatcactgctgg
tatggg
aggaggctctggaactggagctgctcctgttattgctcgtatcgccaaagatttaggtgcgcttacagttggtg
ttgtaa
cacgtccctttggttttgaaggaagtaagcgtggacaatttgctgtagaaggaatcaatcaacttcgtgagcat
gtagac
actctattgattatctcaaacaacaatttgcttgaaattgttgataagaaaacaccgcttttggaggctcttag
cgaagc
ggataacgttcttcgtcaaggtgttcaagggattaccgatttgattaccaatccaggattgattaaccttgact
ttgccg
atgtgaaaacggtaatggcaaacaaagggaatgctcttatgggtattggtatcggtagtggagaagaacgtgtg
gtagaa
gcggcacgtaaggcaatctattcaccacttcttgaaacaactattgacggtgctgaggatgttatcgtcaacgt
tactgg
tggtcttgacttaaccttgattgaggcagaagaggcttcacaaattgtgaaccaggcagcaggtcaaggagtga
acatct
ggctcggtacttcaattgatgaaagtatgcgtgatgaaattcgtgtaacagttgttgcaacgggtgttcgtcaa
gaccgc
gtagaaaaggttgtggctccacaagctagatctgctactaactaccgtgagacagtgaaaccagctcattcaca
tggctt
tgatcgtcattttgatatggcagaaacagttgaattgccaaaacaaaatccacgtcgtttggaaccaactcagg
catctg
cttttggtgattgggatcttcgccgtgaatcgattgttcgtacaacagattcagtcgtttctccagtcgagcgc
tttgaa
gccccaatttcacaagatgaagatgaattggatacacctccatttttcaaaaatcgttaa-3′
(B)
Streptococcus pneumoniae
ftsZ polypeptide sequence deduced from a polynucleotide
sequence in this table[SEQ ID NO:2].
NH
2
-
MTFSFDTAAAQGAVIKVIGVGGGGGNAINRMVDEGVTGVEFIAANTDVQALSSTKAETVIQLGPKLTRGLGAGG
QPEVGR
KAAEESEETLTEAISGADMVFITAGMGGGSGTGAAPVIARIAKDLGALTVGVVTRPFGFEGSKRGQFAVEGINQ
LREHVD
TLLIISNNNLLEIVDKKTPLLEALSEADNVLRQGVQGITDLITNPGLINLDFADVKTVMANKGNALMGIGIGSG
EERVVE
AARKAIYSPLLETTIDGAEDVIVNVTGGLDLTLIEAEEASQIVNQAAGQGVNIWLGTSIDESMRDEIRVTVVAT
GVRQDR
VEKVVAPQARSATNYRETVKPAHSHGFDRHFDMAETVELPKQNPRRLEPTQASAFGDWDLRRESIVRTTDSVVS
PVERFE
APISQDEDELDTPPFFKNR-COOH
(C)
Streptococcus pneumoniae
ftsZ ORF sequence[SEQ ID NO:3].
5′-TCTGCTCCTGTTATTGCTCGTATCGCCAAAGATTTAGGTGCGCTTACAGTTGGTGTTGTA
ACACGTCCCTTTGGTTTTGAAGGAAGTAAGCGTGGACAATTTGCTGTAGAAGGAATCGAT
CAACTTCGTGAGCATGTAGACACTCTATTGATTATCTCAAACAACAATTTGCTTGAAATT
GTTGATAAGAAAACACCGCTTTTGGAGGCTCTTAGCGAAGCGGATAACGTTCTTCGTCAA
GGTGTTCAAGGGATTACCGATTTGATTACCAATCCAGGATTGATTAACCTTGACTTTGCC
GATGTGAAAACGGTAATGGCAAACAAAGGGAATGCTCTTATGGGTATTGGTATCGGTAGT
GGAGAAGAACGTGTGGTAGAAGCGGCACGTAAGGCAATCTATTCACCACTTCTTGAAACA
ACTATTGACGGTGCTGAGGATGTTATCGTCAACGTTACTGGTGGTCTTGACTTAACCTTG
ATTGAGGCAGAAGAGGCTTCACAAATTGTGAACCAGGCAGCAGGTCAAGGAGTGAACATC
TGGCTCGGTACTTCAATTGATGAAAGTATGCGTGATGAAATT
Fueyo Joanna Lynn
Lonetto Michael Arthur
Deibert Thomas S.
Gimmi Edward R.
King William T.
Navarro Albert
SmithKline Beecham Corporation
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