Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Bacterium or component thereof or substance produced by said...
Reexamination Certificate
1999-10-01
2003-04-29
Minnifield, Nita (Department: 1645)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Bacterium or component thereof or substance produced by said...
C424S234100, C424S184100, C424S185100, C514S002600, C530S300000, C530S324000, C530S325000, C530S326000, C530S350000
Reexamination Certificate
active
06555115
ABSTRACT:
TECHNICAL FIELD
The present invention relates generally to the detection and treatment of Chlamydial infection. In particular, the invention is related to polypeptides comprising a Chlamydia antigen and the use of such polypeptides for the serodiagnosis and treatment of Chlamydial infection.
BACKGROUND OF THE INVENTION
Chlamydiae are intracellular bacterial pathogens that are responsible for a wide variety of important human and animal infections.
Chlamydia trachomatis
is one of the most common causes of sexually transmitted diseases and can lead to pelvic inflammatory disease (PID), resulting in tubal obstruction and infertility.
Chlamydia trachomatis
may also play a role in male infertility. In 1990, the cost of treating PID in the US was estimated to be $4 billion. Trachoma, due to ocular infection with
Chlamydia trachomatis,
is the leading cause of preventable blindness worldwide.
Chlamydia pneumonia
is a major cause of acute respiratory tract infections in humans and is also believed to play a role in the pathogenesis of atherosclerosis and, in particular, coronary heart disease. Individuals with a high titer of antibodies to
Chlamydia pneumonia
have been shown to be at least twice as likely to suffer from coronary heart disease as seronegative individuals. Chlamydial infections thus constitute a significant health problem both in the US and worldwide.
Chlamydial infection is often asymptomatic. For example, by the time a woman seeks medical attention for PID, irreversible damage may have already occurred resulting in infertility. There thus remains a need in the art for improved vaccines and pharmaceutical compositions for the prevention and treatment of Chlamydia infections. The present invention fulfills this need and further provides other related advantages.
SUMMARY OF THE INVENTION
The present invention provides compositions and methods for the diagnosis and treatment of Chlamydia infection. In one aspect, polypeptides are provided comprising an immunogenic portion of a Chlamydia antigen, or a variant of such an antigen. In one embodiment, the antigen comprises an amino acid sequence encoded by a DNA sequence selected from the group consisting of (a) a sequence of SEQ ID NO: 1, 15, 21-25, 44-64, 66-76 or 79-88; (b) the complements of said sequences; and (c) sequences that hybridize to a sequence of (a) or (b) under moderately stringent conditions. In a specific embodiment, a polypeptide comprising an amino acid sequence of SEQ ID NO: 5 is provided.
In a related aspect, polynucleotide sequences encoding the above polypeptides, recombinant expression vectors comprising one or more of these polynucleotide sequences and host cells transformed or transfected with such expression vectors are also provided.
In another aspect, the present invention provides fusion proteins comprising an inventive polypeptide, or, alternatively, an inventive polypeptide and a known Chlamydia antigen. In yet another aspect, the present invention provides antibodies, both polyclonal and monoclonal, that bind to the polypeptides described above.
Within other aspects, the present invention provides pharmaceutical compositions that comprise one or more Chlamydia polypeptides disclosed herein, or a polynucleotide molecule encoding such a polypeptide, and a physiologically acceptable carrier. The invention also provides vaccines comprising one or more of the disclosed polypeptides and a non-specific immune response enhancer, together with vaccines comprising one or more polynucleotide sequences encoding such polypeptides and a non-specific immune response enhancer.
In yet another aspect, methods are provided for inducing protective immunity in a patient, comprising administering to a patient an effective amount of one or more of the above pharmaceutical compositions or vaccines.
In yet a further aspect, methods for the treatment of Chlamydia infection in a patient are provided, the methods comprising obtaining peripheral blood mononuclear cells (PBMC) from the patient, incubating the PBMC. with a polypeptide of the present invention (or a polynucleotide that encodes such a polypeptide) to provide incubated T cells and administering the incubated T cells to the patient. The present invention additionally provides methods for the treatment of Chlamydia infection that comprise incubating antigen presenting cells with a polypeptide of the present invention (or a polynucleotide that encodes such a polypeptide) to provide incubated antigen presenting cells and administering the incubated antigen presenting cells to the patient. In certain embodiments, the antigen presenting cells are selected from the group consisting of dendritic cells, macrophages, monocytes, B-cells, and fibroblasts. Compositions for the treatment of Chlamydia infection comprising T cells or antigen presenting cells that have been incubated with a polypeptide or polynucleotide of the present invention are also provided.
In further aspects of the subject invention, methods and diagnostic kits are provided for detecting Chlamydia infection in a patient. In one embodiment, the method comprises: (a) contacting a biological sample with at least one of the polypeptides or fusion proteins disclosed herein; and (b) detecting in the sample the presence of antibodies that bind to the polypeptide or fusion protein, thereby detecting Chlamydia infection in the biological sample. Suitable biological samples include whole blood, sputum, serum, plasma, saliva, cerebrospinal fluid and urine. In one embodiment, the diagnostic kits comprise one or more of the polypeptides or fusion proteins disclosed herein in combination with a detection reagent. In yet another embodiment, the diagnostic kits comprise either a monoclonal antibody or a polyclonal antibody that binds with a polypeptide of the present invention.
The present invention also provides methods for detecting Chlamydia infection comprising: (a) obtaining a biological sample from a patient; (b) contacting the sample with at least two oligonucleotide primers in a polymerase chain reaction, at least one of the oligonucleotide primers being specific for a polynucleotide sequence disclosed herein; and (c) detecting in the sample a polynucleotide sequence that amplifies in the presence of the oligonucleotide primers. In one embodiment, the oligonucleotide primer comprises at least about 10 contiguous nucleotides of a polynucleotide sequence peptide disclosed herein, or of a sequence that hybridizes thereto.
In a further aspect, the present invention provides a method for detecting Chlamydia infection in a patient comprising: (a) obtaining a biological sample from the patient; (b) contacting the sample with an oligonucleotide probe specific for a polynucleotide sequence disclosed herein; and (c) detecting in the sample a polynucleotide sequence that hybridizes to the oligonucleotide probe. In one embodiment, the oligonucleotide probe comprises at least about 15 contiguous nucleotides of a polynucleotide sequence disclosed herein, or a sequence that hybridizes thereto.
These and other aspects of the present invention will become apparent upon reference to the following detailed description. All references disclosed herein are hereby incorporated by reference in their entirety as if each was incorporated individually.
Sequence Identifiers
SEQ ID NO: 1 is the determined DNA sequence for the
C. trachomatis
clone 1-B1-66.
SEQ ID NO: 2 is the determined DNA sequence for the
C. trachomatis
clone 4-D7-28.
SEQ ID NO: 3 is the determined DNA sequence for the
C. trachomatis
clone 3-G3-10.
SEQ ID NO: 4 is the determined DNA sequence for the
C. trachomatis
clone 10-C10-31.
SEQ ID NO: 5 is the predicted amino acid sequence for 1-B1-66.
SEQ ID NO: 6 is the predicted amino acid sequence for 4-D7-28.
SEQ ID NO: 7 is a first predicted amino acid sequence for 3-G3-10.
SEQ ID NO: 8 is a second predicted amino acid sequence for 3-G3-10.
SEQ ID NO: 9 is a third predicted amino acid sequence for 3-G3-10.
SEQ ID NO: 10 is a fourth predicted amino acid sequence for 3-G3-10.
SEQ ID NO: 11 is a fifth predicte
Bhatia Ajay
Jen Shyian
Probst Peter
Skeiky Yasir A. W.
Stromberg Erika Jean
Corixa Corporation
Minnifield Nita
Seed Intellectual Property Law Group PLLC
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