Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues
Reexamination Certificate
1999-11-11
2004-11-23
Duffy, Patricia A. (Department: 1645)
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
C530S350000, C530S402000, C530S810000, C530S811000, C530S812000, C530S813000, C530S814000, C530S820000, C530S825000
Reexamination Certificate
active
06822071
ABSTRACT:
STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT
1. Field of the Invention
This invention relates to nucleic acids and polypeptides from
Chlamydia pneumoniae
and to their use in the diagnosis, prevention and treatment of diseases associated with
C. pneumoniae.
2. Background of the Invention
Chlamydiaceae
is a family of obligate intracellular parasite with a tropism for epithelial cells lining the mucus membranes. The bacteria have two morphologically distinct forms, “elementary body” and “reticulate body”. The elementary body is the infectious form, and has a rigid cell wall, primarily of cross-linked outer membrane proteins. The reticulate body is the intracellular, metabolically active form. A unique developmental cycle between these two forms characterizes
Chlamydia
growth.
C. pneumoniae
is a human respiratory pathogen that causes acute respiratory disease, and approximately 10% of community-acquired pneumonia Antibody prevalence studies have shown that virtually everyone is infected with
C. pneumoniae
at some time, and that reinfection is common. In addition to respiratory disease, studies have shown an association of this organism with coronary artery disease. It has been demonstrated in atherosclerotic lesions of the aorta and coronary arteries by immunocytochemistry and by polymerase chain reaction (Kuo et al. (1993)
J Infect Dis
167(4):841-849).
Recent reports have further demonstrated the presence of
C. pneumoniae
in the walls of abdominal aortic aneurysms (Juvonen et al. (1997)
J Vasc Surg
25(3):499-505). Abdominal aortic aneurysms are frequently associated with atherosclerosis, and inflammation may be an important factor in aneurysmal dilatation.
C. pneumoniae
may play a role in maintaining an inflammation and triggering the development of aortic aneurysms.
Muhlestein et al. (1996)
JACC
27:1555-61, reported a differential incidence of
Chlamydia
species within the coronary artery wall of patients with atherosclerosis versus those with other forms of cardiovascular disease. The extremely high rate of possible infection in patients with symptomatic atherosclerotic disease compared to the very low rate in patients with normal coronary arteries or coronary artery disease from chronic transplant rejection provides evidence for a direct link between the atherosclerotic process and
Chlamydia
infection. Because a history of chlamydial infection is so prevalent in the population, the issue of causality remains. On a physiologic and pathologic level, abnormal interactions among endothelial cells, platelets, macrophages and lymphocytes may lead to a cascade of events resulting in acute endothelial damage, thrombosis and repair, chronically leading to the development of atheroma in blood vessels.
C. pneumoniae
is related to other
Chlamydia
species, but the level of sequence similarity is relatively low. Very little is known about the biology of this organism, although it appears to be an important human pathogen. Allelic diversity and structural relationships between specific genes of
Chlamydia
species is described in Kaltenboeck et al. (1993)
J Bacteriol
175(2):487-502; Gaydos et al. (1992)
Infect Immun
60(12):5319-5323; Everett et al. (1997)
Int J Syst Bacteriol
47(2):461-473; and Pudjiatmoko et al. (1997)
Int J Syst Bacteriol
47(2):425-431.
A number of studies have been published describing methods for detection of
C. pneumoniae,
and for distinguishing between
Chlamydia
species. Such methods include PCR detection (Rasmussen et al. (1992)
Mol Cell Probes
6(5):389-394; Holland et al. (1990)
J Infect Dis
162(4):984-987); a simplified polymerase chain reaction-enzyme immunoassay (Wilson et al. (1996) J Appl Bacteriol 80(4):431-438); sequence determination and restriction endonuclease cleavage (Herrmann et al. (1996)
J Clin Microbiol
34(8):1897-1902).
Antigenic and molecular analyses of different
C. pneumoniae
strains is described in Jantos et al. (1997)
Clin Microbiol
35(3):620-623. Some genes of
C. pneumoniae
have been isolated and sequenced. These include the Gro E operon (Kikuta et al. (1991) Infect Immun 59(12):4665-4669); the major outer membrane protein Perez et al. (1991)
Infect Immun
59(6):2195-2199; the DnaK protein homolog (Komak et al. (1991)
Infect Immun
59(2):721-725); as well as a number of ribosomal and other genes.
SUMMARY OF THE INVENTION
This invention provides the genomic sequence of
Chlamydia pneumoniae.
The sequence information is useful for a variety of diagnostic and analytical methods. The genomic sequence may be embodied in a variety of media, including computer readable forms, or as a nucleic acid comprising a selected fragment of the sequence. Such fragments generally consist of an open reading frame, transcriptional or translational control elements, or fragments derived therefrom. Proteins encoded by the open reading frames are useful for diagnostic purposes, as well as for their enzymatic or structural activity.
DEFINITIONS
The term “amino acid” refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code, as well as those amino acids that are later modified, e.g., hydroxyproline, &ggr;-carboxyglutamate, and O-phosphoserine. Amino acid analogs refers to compounds that have the same basic chemical structure as a naturally occurring amino acid, i.e., an &agr; carbon that is bound to a hydrogen, a carboxyl group, an amino group, and an R group., e.g., homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium Such analogs have modified R groups (e.g., norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid. Amino acid mimetics refers to chemical compounds that have a structure that is different from the general chemical structure of an amino acid, but that functions in a manner similar to a naturally occurring amino acid.
Amino acids may be referred to herein by either their commonly known three letter symbols or by the one-letter symbols recommended by the IUPAC-IUB Biochemical Nomenclature Commission. Nucleotides, likewise, may be referred to by their commonly accepted single-letter codes.
“Amplification” primers are oligonucleotides comprising either natural or analogue nucleotides that can serve as the basis for the amplification of a select nucleic acid sequence. They include, e.g., polymerase chain reaction primers and ligase chain reaction oligonucleotides.
“Antibody” refers to an immunoglobulin molecule able to bind to a specific epitope on an antigen. Antibodies can be a polyclonal mixture or monoclonal. Antibodies can be intact immunoglobulins derived from natural sources or from recombinant sources and can be immunoreactive portions of intact immunoglobulins. Antibodies may exist in a variety of forms including, for example, Fv, F
ab
, and F(ab)
2
, as well as in single chains. Single-chain antibodies, in which genes for a heavy chain and a light chain are combined into a single coding sequence, may also be used.
An “antigen” is a molecule that is recognized and bound by an antibody, e.g., peptides, carbohydrates, organic molecules, or more complex molecules such as glycolipids and glycoproteins. The part of the antigen that is the target of antibody binding is an antigenic determinant and a small functional group that corresponds to a single antigenic determinant is called a hapten.
“Biological sample” refers to any sample obtained from a living or dead organism. Examples of biological samples include biological fluids and tissue specimens. Such biological samples can be prepared for analysis of the presence of
C. pneumoniae
nucleic acids, proteins, or antibodies specifically reactive with the proteins.
The term “
C. pneumoniae
gene” shall be intended to mean the open reading frame encoding specific
C. pneumoniae
polypeptides, as well as adjacent 5′ and 3&p
Davis Ronald
Kalman Sue S.
Mitchell Wayne
Stephens Richard S.
Duffy Patricia A.
The Regents of the University of California
Townsend and Townsend and Crew
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