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
1998-10-19
2001-07-17
Allen, Marianne P. (Department: 1631)
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
C536S023700, C435S006120, C435S320100, C435S325000, C435S253300
Reexamination Certificate
active
06261802
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 ups (undecaprenyl diphosphate synthase) family, as well as their variants, hereinafter referred to as “ups(ugc),” “(ugc) polynucleotide(s),” and “ups (ugc) polypeptide(s)” as the case may be.
BACKGROUND OF THE INVENTION
The frequency of
Pseudomonas aeruginosa
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
Pseudomonas aeruginosa
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 under going 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 ups (ugc) 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 ups (ugc), in particular ups (ugc) polypeptides and ups (ugc) 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 ups (ugc) 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 ups (ugc) polypeptides and polynucleotides as described in greater detail below. In particular, the invention relates to polypeptides and polynucleotides of a ups (ugc) of
Pseudomonas aeruginosa
which is related by amino acid sequence homology to
Micrococcus luteus
Ups (ugc) polypeptide. The invention relates especially to ups (ugc) having the nucleotide and amino acid sequences set out in Table 1 as SEQ ID NO:1and SEQ. ID NO:2 respectively. Note that sequences recited in the Sequence Listing below as “DNA” represents 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
Ups (ugc) Polynucleotide and Polypeptide Sequences
(A)
Pseudomonas aeruginosa
ups (ugc) polynecleotide sequence
[SEQ ID NO:1].
5′-ATGGAAAAGACCCGGAAGGATGTGTGCGTGCCACGCCACGTGGCCATTATCATGGACGGT
AACAATCGCTGGGCGAAGAAGCGTCTTCTGCCCGGCGTCGCCGGCCACAAGGCCGGTGTC
GATGCCGTCAGGGCGGTGATCGAGGTCTGCGCCGAGGCAGGGGTCGAGGTCCTCACCCTG
TTCGCGTTCTCCAGCGAGAACTGGCAGCGTCCGGCGGACGAAGTCAGCGCGCTGATGGAG
CTGTTTCTCGTGGCCCTGCGCCGCGAGGTGCGCAAGCTCGACGAGAACGGCATCCGCCTG
CGCATCATCGGCGATCGCACGCGTTTCCATCCGGAGTTGCAGGCGGCCATGCGCGAAGCG
GAAGCCGCCACTGCCGGCAATACCCGTTTCCTCCTCCAGGTCGCCGCCAACTACGGCGGC
CAGTGGGACATCGTCCAGGCCGCACAGCGCCTGGCGCGCGAGGTCCAGGGCGGGCACCTG
GCGGCGGACGATATCTCCGCCGAGCTGCTCCAGGGCTGCCTGGTGACCGGCGACCAGCCG
CTGCCCGACCTGTGCATCCGCACCGGCGGCGAGCATCGCATCAGCAATTTCCTTCTCTGG
CAGCTGGCCTACGCCGAGCTGTATTTCTCCGACCTGTTCTGGCCCGACTTCAAGCACGCG
GCGATGCGGGCTGCCCTGGCGGATTTCTCCAAGCGCCAGCGCCGCTTCGGCAAGACCAGC
GAGCAAGTCGAGGCCGAAGCCCGTCCGTCATGCTGA
-3′
(B)
Pseudomonas aeruginosa
ups (ugc) polypeptide sequence deduced
from a polynucleotide sequence in this table [SEQ ID NO:2].
NH
2
-MEKTRKDVCVPRHVAIIMDGNNRWAKKRLLPGVAGHKAGVDAVRAVIEVCAEAGVEVLTL
FAFSSENWQRPADEVSALMELFLVALRREVRKLDENGIRLRIIGDRTRFHPELQAAMREA
EAATAGNTRFLLQVAANYGGQWDIVQAAQRLAREVQGGHLAADDISAELLQGCLVTGDQP
LPDLCIRTGGEHRISNFLLWQLAYAELYFSDLFWPDFKHAAMRAALADFSKRQRRFGKTS
EQVEAEARPSC-COOH
Polypeptides
Ups (ugc) polypeptide of the invention is substantially phylogenetically related to other proteins of the ups (undecaprenyl diphosphate synthase) family.
In one aspect of the invention there are provided polypeptides of
Pseudomonas aeruginosa
referred to herein as “ups (ugc)” and “ups (ugc) polypeptides” as well as biologically, diagnostically, prophylactically, clinically or therapeutically useful variants thereof, and compositions comprising the same.
Among the particularly preferred embodiments of the invention are variants of ups (ugc) polypeptide encoded by naturally occurring alleles of the ups (ugc) gene.
The present invention further provides for an isolated polypeptide which: (a) comprises of consists of and amino acid sequence which has at least 70% identity, preferable at least 80% identity, more preferably at least 90% identity, yet more preferably at least 95% identity, most preferably at least 97-99% or exact identity, to that of SEQ ID NO:2 over the entire length of SEQ ID NO:2; (b) a polypeptide encoded by an isolated polynucleotide comprising or consisting of a polynucleotide sequence which has at least 70% identity, preferably at least 80% identity, more preferably at least 90% identity, yet more preferably at least 95% identity, even more preferably at least 97-99% or exact identity to SEQ ID NO:1 over the entire length of SEQ ID NO:1; (c) a polypeptide encoded by an isolated polynucleotide comprising or consisting of polynucleotide sequence encoding a polypeptide which has a least 70% identity, preferably at least 80% identity, more preferably at least 90% identity, yet more preferably at least 95% identity, even more preferably at least 97-99% or exact identity, to the amino acid sequence of SEQ ID NO:2, over the entire length of SEQ ID NO:2.
The polypeptides of the invention include a polypeptide of Table 1 [SEQ ID NO:2] (in particular the mature polypeptide) as well as polypeptides and fragments, particularly those which have the biological activity of ups (ugc), and also those which have at least 70% identity to a polypeptide of Table 1 [SEQ ID NO:1] or the relevant portion, preferably at least 89% identity to a polypeptide of Table 1 [SEQ ID NO:2] and more preferably at least 90% identity to a polypeptide of Table 1 [SEQ ID NO:2] and still more preferably at least 95% identity to a polypeptide of Table 1 [SEQ ID NO:2] and also include portions of such polypeptides with such portion of the polypeptide generally containing at least 30 amino acids and more
Huang Jianzhong
Jiang Xinhe
McDevitt Damien
Traini Christopher M.
Allen Marianne P.
Diebert Thomas S.
Gimmi Edward R.
King William T.
SmithKline Beecham Corporation
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