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
2000-04-11
2002-02-12
Graser, Jennifer E. (Department: 1645)
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
C536S023700, C536S024320, C435S069300, C435S071100, C435S320100, C435S243000, C435S252300
Reexamination Certificate
active
06346397
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 Gyrase family, as well as their variants, hereinafter referred to as “gyrA,” “gyrA polynucleotide(s),” and “gyrA 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.
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 gyrA 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 gyrA protein.
SUMMARY OF THE INVENTION
The present invention relates to gyrA, in particular gyrA polypeptides and gyrA 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 gyrA 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 gyrA polypeptides and polynucleotides as described in greater detail below. In particular, the invention relates to polypeptides and polynucleotides of a gyrA of
Streptococcus pneumoniae
, which is related by amino acid sequence homology to gyrA polypeptide. The invention relates especially to gyrA 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
gyrA Polynucleotide and Polypeptide Sequences
(A)
Streptococcus pneumoniae
gyrA polynucleotide sequence
[SEQ ID NO: 1].
5′- TTGCAACAGCAGCTCAAAGAAGCAAANTGATAAAGCGCAAAAAGATAAGATTCAAGAAGA
TTTGGAAAAACGTTTAGAAGAAAATAAACTCATTCATAAAGAAAAACTAGAACAAACACT
CAAAAAAGAAGTGGAAAAAATGCCTGAGAAATTTATCGAACAGGTTGAGATAAAACGTGT
GGAACAGTTGAAACAATCAGCTCAAGATGAAATTCGTGACCATTTACGAGGGTTTGCAAG
AACAATTCCAAGTTTTATTATGGCTTACGGTGATCAAACTCTAACACTTGATAATTTTGA
TGCCTTTGTTCCTGAACATGTTTTTTATGAAGTAACAGGGATTACGATTGATCAGTTTAG
ATATTTGCGAGATGGTGGGCAGGATTTTGCCAGGGCATCTCTTTGATAAAGCAACATTTG
ACGAAGCTATTCAAGAATTTCTTCGCAAGAAAAAGGAGTTGGCGGATTATTTTAAAGATC
AAAAAGAAGACATTTTTGACTATATTCCACCGCAGAAGACCAACCAAATTTTCACTCCTA
AACGAGTGGTGAAAAGGATGGTAGATGATTTGGAAAAGGAAAATCCAGGGATTTTTGATG
ATCCATCTAAGACTTTTATTGATTTATATATGAAGTCAGGCCTCTATATTGCAGAACTTG
TGAAGCGGTTATATAATAGCAATGGCTTGAAAGAGGCCTTTCCAAATCCTGAAGAACGCT
TAAAACATATTTTGGAAAAGCAAGTTTATGGATTTGCTCCGTCTGAGATTATCTATAACA
TTTCCACTAATTTTATATTTGGTAATCTTTCTAAAGATATCAGTAGGAAGAATTTTGTTT
TAGCAGATACCATTCCAGCGGCTAAAGAAGGGAGCATTCAAAAGTTGGTTGATTCCTATT
TTGAAAATAATTAAAAAGAAGGCCGAGTCAAAATTCTTTGAAATCAGAAAAAACGCATAA
TATTGAGTGCTTTTGTACTGCCCCCCAAAAGTTAGACAGAAAAAATCTAACTTTTGGGGG
GCAGTTCAGACAATCCCTTGGTATTATGCGTTTTATTGTGGGAAGATGTATAATGGATTG
AAATAAGATATGAACAAATCGATTAGGAAAGGAAAATTGATTTATAGAAATGTTTTAGTA
GTCGGATGCGTACTGTTATAGATTCAACGAACTATAAAATCTGAAGAAAGCAATTTTAAC
CAGATCTTAGAAGCAGTTGTGTACTACTCTAACTTCAATAGACTATATCATATAGATAAA
AAACAACTCCCTGATGATTCAAGGAGTTGTCTATAGTTAAATTAGTTTTTAGAAGCTTCT
TGGAATTCTGGATTTTTCCATGCTTCGTCAATAATAGCTTGCAATTCTTTAGCAGATGCT
TGCATTTTTTGAGTTTCTGCATCGTTCAATGGAATGTTTACTGGACGAACGATACCATGT
GCACCAACAACAGCTGGTTGACCGATAAAGACATTCTCAACTCCGTATTGACCTTCTTGG
AATACTGAAAGTGGAAGTATGCGTTTTCATCGTCAAGGATTGCTTTAGTGATACGAGCAA
GGGCTACTGCGATACCGTAGTATGTTGCACCTTTTTTGTTGATGATTGTGTAGGCTGCAT
CACGAACACCTTCGAACAATTCAATCAATTCAGCTTCTTGAACATTTTGAGTGTCTTTAA
GGAATTCTTCAAGGTTTACACCAGCGATGTTAGCGTGTGACCAAACAGCGAACTCAGAGT
CACCGTGTTCACCCATGATGTAGGCGTGCACTGAACGAGCATCCACATCCAATTTTTCAG
CAAGTGCTTGACGGAAACGAGCTGAGTCAAGTGAAGTACCTGAACCGATAACGCGTTCTT
TAGGGAAACCAGAGAATTTCCAAGTTGAGTAAGTCAAAACGTCAACTGGGTTAGCAGCAA
CAAGGAAGATACCTTTGAAACCAGATTCAACAACTTGAGTTACGATTGATTTGTTGATAG
CAAGGTTTTTACCTACAAGGTCAAGACGAGTTTCACCTGGTTTTTGAGGTGCACCTGCAG
TGATTACAACAAGGTCAGCGTCTGCACAGTCAGAGTATTGAGCTGCATAGATTTTTTTAG
GTGAAGTGAAGGCAAGGGCGTGACTAAGGTCAAGCGCATCACCAACAGCTTTTTCATGCA
ATTGTGGAATTTCGATAATTCCAAGCTCTTGTGCAATTCCTTGGTTAACAAGTGCAAAAG
CGTAAGATGAACCTACAGCACCATCACCGACAAGGATAACTTTTTTGTGTTGTTTAGTYR
RAGTCATTGTTTTAAMCATCTCCTTAATTYTATTAGGGGATTTTCCCTAGACAACTTCAT
TCTATCACTTTTAAAAAACTTTGTCACGAATATGCCTTATAGTTCTCGATGTAAACGTTT
TAGTGGTTTAGAGGCTGAAATAGATGGGAATTTATGGTATAATGTTGTTACTTACTAATT
GTGAAATGAGGCATTTATTAATGCAGGATAAAAATTTAGTGAATGTCAATCTGACAAAGG
AGATGAAGGCAAGTTTTATCGACTACGCCATGAGTGTTATCGTAGCGCGAGCTCTTCCTG
ATGTTCGAGATGGCTTAAAACCTGTTCACCGTCGCATTCTCTACGGAATGAATGAATTGG
GTGTGACCCCAGACAAACCCCATAAAAAATCTGCTCGTATTACAGGGGATGTCATGGGTA
AATAYCACCCACACGGGGATTCCTCTATTTATGAAGCCATGGTCCGTATGGCTCAATGGT
GGAGCTACCGTTACATGCTTGTAGATGGTCATGGGAATTTTGGTTCCATGGATGGAGATA
GTGCTGCCGCTCAACGTTATACCGAGGCACGTATGAGCAAGATTGCTCTGGAAATGCTTC
GTGATATCAACAAAAATACAGTTGATTTCGTTGATAACTATGATGCCAATGAACGGGAAC
CCTTGGTCTTGCCAGCGCGTTTTCCAAACCTTTTGGTTAATGGAGCAACTGGTATCGCGG
TTGGGATGGCAACCAATATTCCACCTCATAATCTGGGTGAAACCATTGATGCAGTGAAGT
Warren, Jr. Richard Lloyd
Wilding Edwina Imogen
Deibert Thomas S.
Gimmi Edward R.
Graser Jennifer E.
King William T.
SmithKline Beecham Corportion
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