Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues
Reexamination Certificate
1998-08-10
2001-04-24
Bui, Phuong T. (Department: 1645)
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
C530S412000, C530S808000, C530S820000, C530S825000, C435S069100, C435S069700, C435S071100
Reexamination Certificate
active
06222014
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 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
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
Staphylococcus 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 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 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 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 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 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
Staphylococcus aureus
, 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. 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
nrdE Polynucleotide and Polypeptide Sequences
(A)
Staphylococcus aureus
nrdE polynucleotide sequence
[SEQ ID NO: 1].
5′-ATGAAAACCATGGAAGAGAAAAAGTACAATCATATTGAATTAAATAATGA
GGTCACTAAACGAAGAGAAGATGGATTCTTTAGTTTAGAAAAAGACCAAG
AAGCTTTAGTAGCTTATTTAGAAGAAGTAAAAGACAAAACAATCTTCTTC
GATACTGAAATCGAGCGTTTACGTTATTTAGTAGACAACGATTTTTATTT
CAATGTGTTTGATATTTATAGTGAAGCGGATCTAATTGAAATCACTGATT
ATGCAAAATCAATCTCGTTTAATTTTGCAAGTTATATGTCAGCTAGTAAA
TTTTTCAAAGATTACGCTTTGAAAACAAATGATAAAAGTCAATACTTAGA
AGACTATAATCAACACGTTGCCATTGTTGCTTTATACCTAGCAAATGGTA
ATAAAGCACAAGCTAAACAATTTATTTCTGCTATGGTTGAACAAAGATAT
CAACCAGCGACACCAACATTTTTAAACGCAGGCCGTGCGCGTCGTGGTGA
GCTAGTGTCATGTTTCTTATTAGAAGTGGATGACAGCTTAAATTCAATTA
ACTTTATTGATTCAACTGCAAAACAATTAAGTAAAATTGGGGGCGGCGTT
GCAATTAACTTATCTAAATTGCGTGCACGTGGTGAAGCAATTAAAGGAAT
TAAAGGCGTAGCGAAAGGCGTTTTACCTATTGCTAAGTCACTTGAAGGTG
GCTTTAGCTATGCAGATCAACTTGGTCAACGCCCTGGTGCTGGTGCTGTG
TACTTAAATATCTTCCATTATGATGTAGAAGAATTTTTAGATACTAAAAA
AGTAAATGCGGATGAAGATTTACGTTTATCTACAATATCAACTGGTTTAA
TTGTTCCATCTAAATTCTTCGATTTAGCTAAAGAAGGTAAGGACTTTTAT
ATGTTTGCACCTCATACAGTTAAAGAAGAATATGGTGTGACATTAGACGA
TATCGATTTAGAAAAATATTATGATGACATGGTTGCAAACCCAAATGTTG
AGAAAAAGAAAAAGAATGCGCGTGAAATGTTGAATTTAATTGCGCAAACA
CAATTACAATCAGGTTATCCATATTTAATGTTTAAAGATAATGCTAACAG
AGTGCATCCGAATTCAAACATTGGACAAATTAAAATGAGTAACTTATGTA
CGGAAATTTTCCAACTACAAGAAACTTCAATTATTAATGACTATGGTATT
GAAGACGAAATTAAACGTGATATTTCTTGTAACTTGGGCTCATTAAATAT
TGTTAATGTAATGGAAAGCGGAAAATTCAGAGATTCAGTTCACTCTGGTA
TGGACGCATTAACTGTTGTGAGTGATGTAGCAAATATTCAAAATGCACCA
GGAGTTAGAAAAGCTAACAGTGAATTACATTCAGTTGGTCTTGGTGTGAT
GAATTTACACGGTTACCTAGCAAAAAATAAAATTGGTTATGAGTCAGAAG
AAGCAAAAGATTTTGCAAATATCTTCTTTATGATGATGAATTTCTACTCA
ATCGAACGTTCAATGGAAATCGCTAAAGAGCGTGGTATCAAATATCAAGA
CTTTGAAAAGTCTGATTATGCTAATGGCAAATATTTCGAGTTCTATACAA
CTCAAGAATTTGAACCTCAATTCGAAAAAGTACGTGAATTATTCGATGGT
ATGGCTATTCCTACTTCTGAGGATTGGAAGAAACTACAACAAGATGTTGA
ACAATATGGTTTATATCATGCATATAGATTAGCAATTGCTCCAACACAAA
GTATTTCTTATGTTCAAAATGCAACAAGTTCTGTAATGCCAATCGTTGAC
CAAATTGAACGTCGTACTTATGGTAATGCGGAAACATTTTACCCTATGCC
ATTCTTATCACCACAAACAATGTGGTACTACAAATCAGCATTCAATACTG
ATCAGATGAAATTAATCGATTTAATTGCGACAATTCAAACGCATATTGAC
CAAGGTATCTCAACGATCCTTTATGTTAATTCTGAAATTTCTACACGTGA
GTTAGCAAGATTATATGTATATGCGCACTATAAAGGATTAAAATCACTTT
ACTATACTAGAAATAAATTATTAAGTGTAGAAGAATGTACAAGTTGTTCT
ATCTAA-3′
(B)
Staphylococcus aureus
nrdE polypeptide sequence deduced
from a polynucleotide sequence in this table [SEQ ID NO:2].
NH
2
-MKTMEEKKYNHIELNNEVTKRREDGFFSLEKDQEALVAYLEEVKDKTIFF
DTEIERLRYLVDNDFYFNVFDIYSEADLIEITDYAKSISFNFASYMSASK
FFKDYALKTNDKSQYLEDYNQHVAIVALYLANGNKAQAKQFISAMVEQRY
QPATPTFLNAGRARRGELVSCFLLEVDDSLNSINFIDSTAKQLSKIGGGV
AINLSKLRARGEAIKGIKGVAKGVLPIAKSLEGGFSYADQLGQRPGAGAV
YLNIFHYDVEEFLDTKKVNADEDLRLSTISTGLIVPSKFFDLAKEGKDFY
MFAPHTVKEEYGVTLDDIDLEKYYDDMVANPNVEKKKKNAREMLNLIAQT
QLQSGYPYLMFKDNANRVHPNSNIGQIKMSNLCTEIFQLQETSIINDYGI
EDEIKRDISCNLGSLNIVNVMESGKFRDSVHSGMDALTVVSDVANIQNAP
GVRKANSELHSVGLGVMNLHGYLAKNKIGYESEEAKDFANIFFMMMNFYS
IERSMEIAKERGIKYQDFEKSDYANGKYFEFYTTQEFEPQFEKVRELFDG
MAIPTSEDWKKLQQDVEQYGLYHAYR
Black Michael Terence
Traini Christopher M
Wilding Edwina Imogen
Bui Phuong T.
Deibert Thomas S.
Gimmi Edward R.
King William T.
Lee Li
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