Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving hydrolase
Reexamination Certificate
2000-05-22
2002-12-24
Leary, Louise N. (Department: 1623)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving hydrolase
C435S004000
Reexamination Certificate
active
06498017
ABSTRACT:
The present invention relates to a method for the diagnostic detection of diseases associated with pathological protein depositions.
A number of diseases is associated with the occurrence of pathological protein depositions. It is often unclear whether the protein depositions are only manifestations of a clinical picture, or whether such protein depositions themselves are the pathogens and thus the cause of the disease. Thus, neurodegenerative diseases are known in which, for example, protein depositions referred to as amyloid plaques can be detected in the brain of afflicted persons. Such diseases include, for example, Alzheimer's disease, bovine spongiform encephalopathy (BSE), Creutzfeldt-Jakob disease (CJD), laughing death syndrome, scrapie, and possibly other diseases which were referred to as “slow virus” diseases in the past. More recently, the BSE disease, in particular, has become a focus of public attention, which is due to the fact, inter alia, that BSE has been connected with the Creutzfeldt-Jakob disease in humans. Today, the mechanisms by which the protein depositions affect the pathological process are still unclear. The relationship, observed by Prusiner, between infectiosity and the concentration of certain proteins which play a role in the pathological process of scrapie, a neurodegenerative disease in sheep, is remarkable. Pathological protein depositions appear not only in diseases of the neuronal system, but are observed in other organs as well, such as in a disease of diabetes type II.
A survey of prion diseases has been published by D. Riesner in “Chemie in unserer Zeit” (1996), p. 66-74. Inter alia, it is set forth therein that a reliable and quick diagnosis is a priority problem of prion research, not only to ensure biological safety, but also to promote the basic research which involves a lot of open questions as to the replication and pathogenesis of prions. Especially for Alzheimer's disease, the pathological picture has been described relatively well. “Senile plaques”, which substantially consist of aggregated amyloid-&bgr; protein, and “paired helical filaments”, which are constituted of abnormally altered tau protein, are closely connected with Alzheimer's disease. The present state of the art of the biochemical diagnosis of Alzheimer's disease is the immunological concentration measurement of soluble A&bgr; peptides (Motter et al., reduction of &bgr;-amyloid peptide
1-42
in the cerebrospinal fluid of patients with Alzheimer's disease, Ann. Neurol. 38: 643; 1995) or of the soluble tau protein (Vadermeeren et al., Detection of tau proteins in normal and Alzheimer's disease cerebrospinal fluid with a sensitive sandwich enzyme-linked immunosorbent assay, J. Neurochemistry 61: 1828-1834; 1993) in the cerebrospinal fluid. In the U.S. Pat. No. 5,593,846, a method for determining the concentration of soluble amyloid-&bgr; protein has been described. However, the actual pathological component, the protein depositions themselves, cannot be measured with this method.
After having concentrated cerebrospinal fluid, Townsend found structures therein which can be stained with the long known dye thioflavine S which is specific for protein aggregates (Townsend et al., 1987, Neurochemical Pathology,
6, 213-229).
In the corresponding U.S. Pat. No. 5,486,460, a method for diagnosing Alzheimer's disease is described in which concentrated cerebrospinal fluid is plated on a glass surface and, after having dried, stained with thioflavine S. However, this method is inconvenient in practice. In addition, the staining method with thioflavine S is not unambiguous for pathological protein depositions linked with Alzheimer's disease (see above). The method described did not meet with any further attention in the relevant art, and neither did the corresponding publication.
In U.S. Pat. No. 5,434,050, Maggio describes a method for diagnosing Alzheimer's disease by associating A&bgr; peptides to A&bgr; aggregates, which are present as a solid bound structure, e.g., as a brain slice material. However, this diagnostic method can be practiced only post mortem, as in the living patient, it would require a severe surgical intervention for obtaining brain biopsy material.
Therefore, it has long been desired to perform a measurement in body fluids, such as cerebrospinal fluid.
REFERENCES:
patent: 5270165 (1993-12-01), Van Norstrand et al.
patent: WO93/23432 (1993-11-01), None
patent: WO97/10505 (1997-03-01), None
patent: WO97/15685 (1997-05-01), None
Bieschke Jan
Eigen Manfred
Pitschke Martin
Post Karin
Riesner Detlev
Evotec BioSystems AG
Jacobson & Holman PLLC
Leary Louise N.
LandOfFree
Method for measuring the association of substructures 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 Method for measuring the association of substructures of..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for measuring the association of substructures of... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2989863