Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Bacterium or component thereof or substance produced by said...
Reexamination Certificate
1996-08-29
2001-09-04
Swartz, Rodney P. (Department: 1645)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Bacterium or component thereof or substance produced by said...
C424S168100, C424S184100, C424S185100, C424S192100, C435S253100, C435S863000, C514S002600, C514S924000, C530S350000, C536S023400
Reexamination Certificate
active
06284255
ABSTRACT:
TECHNICAL FIELD
The present invention relates generally to the detection, treatment and prevention of infectious diseases. In particular, the invention is related to compounds and methods for the treatment of mycobacterial infections including
Mycobacterium tuberculosis
and
Mycobacterium avium
. The invention is further related to compounds that function as non-specific immune response amplifiers, and the use of such non-specific immune response amplifiers as adjuvants in vaccination or immunotherapy against infectious disease, and in certain treatments for immune disorders and cancer.
BACKGROUND OF THE INVENTION
Tuberculosis is a chronic, infectious disease, that is caused by infection with
Mycobacterium tuberculosis
(
M. tuberculosis
). It is a major disease in developing countries, as well as an increasing problem in developed areas of the world, with about 8 million new cases and 3 million deaths each year. Although the infection may be asymptomatic for a considerable period of time, the disease is most commonly manifested as a chronic inflammation of the lungs, resulting in fever and respiratory symptoms. If left untreated, significant morbidity and death may result.
Although tuberculosis can generally be controlled using extended antibiotic therapy, such treatment is not sufficient to prevent the spread of the disease. Infected individuals may be asymptomatic, but contagious, for some time. In addition, although compliance with the treatment regimen is critical, patient behavior is difficult to monitor. Some patients do not complete the course of treatment, which can lead to ineffective treatment and the development of drug resistant mycobacteria.
Inhibiting the spread of tuberculosis requires effective vaccination and accurate, early diagnosis of the disease. Currently, vaccination with live bacteria is the most efficient method for inducing protective immunity. The most common mycobacterium employed for this purpose is Bacillus Calmette-Guerin (BCG), an avirulent strain of
Mycobacterium bovis
. However, the safety and efficacy of BCG is a source of controversy and some countries, such as the United States, do not vaccinate the general public. Diagnosis of
M. tuberculosis
infection is commonly achieved using a skin test, which involves intradermal exposure to tuberculin PPD (protein-purified derivative). Antigen-specific T cell responses result in measurable induration at the injection site by 48-72 hours after injection, thereby indicating exposure to mycobacterial antigens. Sensitivity and specificity have, however, been a problem with this test, and individuals vaccinated with BCG cannot be distinguished from infected individuals.
A less well-known mycobacterium that has been used for immunotherapy for tuberculosis, and also leprosy, is
Mycobacterium vaccae
, which is non-pathogenic in humans. However, there is less information on the efficacy of
M. vaccae
compared with BCG, and it has not been used widely to vaccinate the general public.
M. bovis
BCG and
M. vaccae
are believed to contain antigenic compounds that are recognized by the immune system of individuals exposed to infection with
M tuberculosis.
There thus remains a need in the art for effective compounds and methods for preventing, treating and detecting tuberculosis.
SUMMARY OF THE INVENTION
Briefly stated, the present invention provides compounds and methods for the prevention, treatment and diagnosis of mycobacterial infection, together with adjuvants for use in vaccines or immunotherapy of infectious diseases and cancers.
In a first aspect, polypeptides derived from
Mycobacterium vaccae
are provided comprising an immunogenic portion of a soluble antigen, or a variant of such an antigen. In one embodiment, the soluble antigen induces an immune response in patients previously exposed to a mycobacterium. In a second embodiment, the soluble antigen includes an amino acid sequence selected from the group consisting of sequences recited in SEQ ID NOS: 4-29, 43-45, 47 and 52-55, and variants thereof.
In another embodiment, the antigen comprises an amino acid sequence encoded by a DNA molecule selected from the group consisting of: sequences recited in SEQ ID NOS: 40-42, 46 and 48-51, and variants thereof; and the complements of said sequences and variants of such complements.
DNA sequences encoding the inventive polypeptides, expression vectors comprising these DNA sequences, and host cells transformed or transfected with such expression vectors are also provided.
In another aspect, the present invention provides fusion proteins comprising a first and a second inventive polypeptide or, alternatively, an inventive polypeptide and a known
M. tuberculosis
antigen.
Within other aspects, the present invention provides pharmaceutical compositions that comprise at least one of the inventive polypeptides, or a DNA molecule encoding such a polypeptide, and a physiologically acceptable carrier. The invention also provides vaccines comprising at least one of the above polypeptides and a non-specific immune response amplifier, together with vaccines comprising at least one DNA sequence encoding such polypeptides and a non-specific immune response amplifier.
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 polypeptides together with an immune response amplifier.
In further aspects of this invention, methods and diagnostic kits are provided for detecting tuberculosis in a patient. In a first embodiment, the method comprises contacting dermal cells of a patient with one or more of the above polypeptides and detecting an immune response on the patient's skin. In a second embodiment, the method comprises contacting a biological sample with at least one of the above polypeptides; and detecting in the sample the presence of antibodies that bind to the polypeptide or polypeptides, thereby detecting
M. tuberculosis
infection in the biological sample. Suitable biological samples include whole blood, sputum, serum, plasma, saliva, cerebrospinal fluid and urine.
Diagnostic kits comprising one or more of the above polypeptides in combination with an apparatus sufficient to contact the polypeptide with the dermal cells of a patient are provided. The present invention also provides diagnostic kits comprising one or more of the inventive polypeptides in combination with a detection reagent.
In yet another aspect, the present invention provides antibodies, both polyclonal and monoclonal, that bind to the polypeptides described above, as well as methods for their use in the detection of
M. tuberculosis
infection.
The present invention also provides methods for enhancing a non-specific immune response to an antigen, comprising administering
M. vaccae
culture filtrate or delipidated
M. vaccae
cells.
These and other aspects of the present invention will become apparent upon reference to the following detailed description and attached drawings. All references disclosed herein are hereby incorporated by reference in their entirety as if each was incorporated individually.
REFERENCES:
patent: 3956481 (1976-05-01), Jolles et al.
patent: 4036953 (1977-07-01), Adam et al.
patent: 4716038 (1987-12-01), Stanford et al.
patent: 4724144 (1988-02-01), Rook et al.
patent: 4879213 (1989-11-01), Fox et al.
patent: 5599545 (1997-02-01), Stanford et al.
patent: 0763361 (1997-03-01), None
patent: 9007935 (1990-07-01), None
patent: 9101751 (1991-02-01), None
patent: 9102542 (1991-03-01), None
patent: 9208488 (1992-05-01), None
patent: 9208484 (1992-05-01), None
patent: 9316727 (1993-09-01), None
patent: 9406466 (1994-03-01), None
patent: 9514713 (1995-06-01), None
patent: 9526742 (1998-03-01), None
patent: 9526742 (2001-03-01), None
Smith, Elements of Molecular Neurobiology, 2nd edition, p.48-50, 1996.*
Khandekar et al. Int. J. Lepr. Other Mycobact Dis. Sep. 1986, 54(3), 416-22.*
Lazar et al. Mol. & Cell. Biol. 1988 8 (3), 1247-1252.*
Burgess et al. J. Cell. Biol. 1990, 111, 2129-2138.*
R.G. White
Hiyama Jun
Scott Linda
Tan Paul
Visser Elizabeth
Genesis Research & Development Corporation Limited
Sleath Janet
Speckman Ann W.
Swartz Rodney P.
LandOfFree
Compounds and methods for treatment and diagnosis of... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Compounds and methods for treatment and diagnosis of..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Compounds and methods for treatment and diagnosis of... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2443899