Chemistry: molecular biology and microbiology – Vector – per se
Reexamination Certificate
1998-06-05
2003-12-09
Martinell, James (Department: 1632)
Chemistry: molecular biology and microbiology
Vector, per se
C435S325000, C435S252300, C536S023500
Reexamination Certificate
active
06660520
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 nrdE (ribonucleotide diphosphate reductase) family, as well as their variants, hereinafter referred to as “nrdE,” “nrdE polynucleotide(s),” and “nrdE 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
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.
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 nrdE 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 nrdE protein.
SUMMARY OF THE INVENTION
The present invention relates to nrdE, in particular nrdE polypeptides and nrdE 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 nrdE 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 nrdE polypeptides and polynucleotides as described in greater detail below. In particular, the invention relates to polypeptides and polynucleotides of a nrdE of
Streptococcus pneumoniae
, which is related by amino acid sequence homology to nrdE polypeptide. The invention relates especially to nrdE 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
nrdE Polynucleotide and Polypeptide Sequences
(A) Streptococcus pneumoniae nrdE polynucleotide
sequence [SEQ ID NO:1].
5′-ATGGGATTAAAACATCTTGAAGACGTGACTTACTTCCGTCTTAATA-
ACGA
AATTAACCGTCCTGTTAATGGACAAATCATGCTTCATAAAGATAAGGAAG
CCTTGGATGCTTTCTTTAAAGAAAATGTAGTTCCAAACACTATGGTTTTT
GATTCAATCAAAGACAAAATCAATTACCTCATTGAACACAACTACATCGA
AACAGCCTTTATCAAGAAATACCGTCCAGAGTTCTTGGAAGAATTGGCTC
AATTTATCAAAGACCAAAACTTCCAATTCAAGTCATTCATGGCAGCTTAT
AAATTTTACAATCAATATGCCTTAAAGACTAATGACGGTGAATACTATCT
TGAAAATATGGAAGACCGTGTCTTCTTCAACGCCCTTTATTTCGCTGATG
GGAATGAAGCTGTTGCAATCGATATTGCCAATGAAATCATCCACCAACGC
TACCAACCTGCTACTCCTTCCTTCTTGAATGCTGGACGTGCTCGTCGTGG
GGAGTTGGTATCTTGTTTCCTAATCCAAGTGACGGATGATATGAACTCTA
TCGGACGTTCTATCAACTCAGCTCTTCAACTTTCACGTATTGGTGGTGGT
GTGGGAATTACCCTCAGCAACCTTCGTGAAGCTGGTGCACCTATCAAAGG
CTATGAAGGAGCTGCTTCAGGTGTCGTTCCTGTTATGAAGCTTTTTGAAG
ACAGCTTCTCTTACTCCAACCAATTGGGGCAACGTCAAGGTGCCGGTGTT
GTCTACCTCAACGTCTTTCACCCAGATATCATCGCTTTCCTTTCAACTAA
GAAAGAAAACGCTGATGAAAAAGTACGTGTCAAGACTCTATCACTTGGTG
TTGTAGTACCTGATAAATTCTACGAATTGGCTCGTAAAAATGAAGAAATG
TACCTCTTCAGCCCTTACTCTGTAGAAAAAGAATACGGTGTGCCATTCAA
TTACATCGACATTACTGAAAAATACGATGAATTGGTCGCAAATCCAAATA
TTCGCAAGACAAAAATCAAGGCGCGGGATTTGGAAACTGAAATCTCTAAA
TTGCAACAAGAGTCTGGCTATCCTTATGTAGTCAACATAGATACGGCTAA
CCGTGCAAATCCTGTTGATGGAAAGATTATCATGAGTAACTTGTGTTCTG
AGATTCTTCAAGTTCAAGAACCAAGCTTGATCAACGATGCTCAAGAATTC
CTTCAAATGGGAACAGATGTTTCATGTAACCTGGGTTCAACCAACGTGGT
TAACATGATGACTTCACCTGATTTTGGTCGTTCTATCCGTGCTATGGTTC
GTGCCCTTACTTTCGTTACAGATAGTTCACATATCGTAGCTGTACCAACG
ATTGACCATGGAAATAGCCAAGCCCACACCTTTGGTCTCGGTGCCATGGG
ACTGCACAGCTACCTTGCCCAACAACTCATTGAATATGGTTCACCTGAGT
CTGTTGAATTTACAAGCATCTACTTTATGCTTATGAACTACTGGACCTTG
GTAGAGTCAAACAATATTGCGCGTGAACGTGGTATTACCTTCCACAACTT
TGAAAAATCAGACTATGCTAACGGAAGTTACTTTGACAAGTATGTAACTG
GTGAATTTGTTCCAACATCAGACCGTGTTAAAGAACTCTTCAAAAATGTC
TTTATCCCTGGTGTTGCTGATTGGGCTGAACTTCGGGACAAGGTTCAAGA
AGATGGTCTTTACCACCAAAATCGCCTTGCTGTAGCGCCAAATGGTTCTA
TCAGCTATATCAACGACGTTTCTGCTTCTATCCACCCGATTACGCAACGT
ATCGAAGAACGCCAAGAGAAGAAAATTGGTAAAATCTACTACCCTGCTGC
TGGCTTGTCTACAGAAACCATTCCTTACTACACTTCTGCCTACGATATGG
ATATGCGTAAAGTCATCGATGTTTACGCTGCTGCGACTGAACACGTGGAT
CAAGGACTTTCACTCACCCTCTTCATGCGTAGTGACATTCCAAAAGGCCT
TTACGAATGGAAGAGGGAAAATAAACAAACGACACGTGACTTGTCCATCC
TTCGTAACTATGCCTTTAACAAGGGAATCAAGTCTATCTACTACGTCCGT
ACCTTTACAGATGACGGTGGAGAAGTCGGCGCCAACCAATGTGAAAGCTG
TGTGATTTAG-3′
(B) Streptococcus pneumoniae nrdE polypeptide
sequence deduced from a polynucleotide
sequence in this table [SEQ ID NO:2].
NH
2
-MGLKHLEDVTYFRLNNEINRPVNGQIMLHKDKEALDAFFKENVVP-
NTMVF
DSIKDKINYLIEHNYIETAFIKKYRPEFLEELAQFIKDQNFQFKSFMAAY
KFYNQYALKTNDGEYYLENMEDRVFFNALYFADGNEAVAIDIANEIIHQR
YQPATPSFLNAGRARRGELVSCFLIQVTDDMNSIGRSINSALQLSRIGGG
VGITLSNLREAGAPIKGYEGAASGVVPVMKLFEDSFSYSNQLGQRQGAGV
VYLNVFHPDIIAFLSTKKENADEKVRVKTLSLGVVVPDKFYELARKNEEM
YLFSPYSVEKEYGVPFNYIDITEKYDELVANPNIRKTKIKARDLETEISK
LQQESGYPYVVNIDTANRANPVDGKIIMSNLCSEILQVQEPSLINDAQEF
LQMGTDVSCNLGSTNVVNMMTSPDFGRSIRAMVRALTFVTDSSHIVAVPT
IDHGNSQAHTFGLGAMGLHSYLAQQLIEYGSPESVEFTSIYFMLMNYWTL
VESNNIARERGITFHNFEKSDYANGSYFDKYVTGEFVPTSDRVKELFKNV
FIPGVADWAELRDKVQEDGLYHQNRLAVAPNGSISYINDVSASIHPITQR
IEERQEKKIGKIYYPAAGLSTETIPYYTSAYDMDMRKVIDVYAAATEHVD
QGLSLTLFMRSDIPKGLYEWKRENKQTTRDLSILRNYAFNKGIKSIYYVR
TFTDDGGEVGANQCESCVI-COOH
Deposited Materials
A deposit containing a
S
Black Michael Terence
Jaworski Deborah Dee
Kosmatka Anna Lisa
Shilling Lisa Kathleen
Wang Min
Fedon Jason C.
Gimmi Edward R.
Kinzig Charles M.
Martinell James
SmithKline Beecham Corporation
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