Method of binding material to the &bgr;-amyloid peptide

Details Method of binding material to the &bgr;-amyloid peptide Method of binding material to the &bgr;-amyloid peptide

1996-10-21

2001-09-25

Chin, Christopher L. (Department: 1641)

Chemistry: molecular biology and microbiology

Measuring or testing process involving enzymes or...

Involving antigen-antibody binding, specific binding protein...

C435S007800, C435S007900, C435S007950, C435S040500, C436S512000, C436S518000, C436S536000, C436S063000, C436S804000, C530S391100, C530S810000, C530S839000

Reexamination Certificate

active

06294340

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to Alzheimer's disease, and particularly relates to methods of binding antigenic compounds to the &bgr;-amyloid peptide found in the senile plaques of Alzheimer's disease.
BACKGROUND OF THE INVENTION
The senile amyloid plaques and congophilic angiopathic lesions found in abundance in brain of patients with Alzheimer's disease are abnormal extracellular structures. The biochemical composition of these structures has been extensively studied to better understand their possible role in the pathogenesis of this dementing disease. The mature amyloid plaque is a complex structure, consisting of a central core of amyloid fibrils surrounded by dystrophic neurites, axonal terminals and dendrites, microglia and fibrous astrocytes. The amyloid core of the senile amyloid plaque, and which surrounds blood vessels to produce the congophilic angiopathy, is a peptide of 39 to 43 amino acids termed the &bgr;-Amyloid (&bgr;A) peptide, the A&bgr; peptide, the A4 protein, or the &bgr;A4 peptide. &bgr;A peptide is found in the brain in Alzheimer's disease, Down's syndrome, hereditary cerebral hemorrhage of the Dutch type, and in old age. See, e.g., K. Kosik
Science
256, 780-783 (1992).
E. Kline et al., PCT Appln WO 91/16819 describes a method of treating Alzheimer's disease by administering the &bgr;-amyloid peptide itself, or an active fragment thereof. H. Potter, PCT Appln WO 92/03474, describes a therapeutic method of treating individuals, such as Alzheimer's disease patients, to prevent the formation of an &agr;-antichymotrypsin-&bgr;-amyloid peptide complex by administering to the subject a synthetic peptide comprising a fragment of the &bgr;-amyloid peptide.
The &bgr;A peptide is produced by the abnormal proteolytic processing of a larger protein, the amyloid precursor protein (APP). APP itself has been identified in the senile amyloid plaque, and additional proteins which have been localized to senile amyloid plaques and angiopathic lesions include apolipoprotein E, alpha-1-antichymotrypsin, complement factors C1q and C3q, APP, and IgG. See, e.g., W. Strittmatter et al.,
Proc. Natl. Acad. Sci
. 90, 1977 (1993); Abraham et al., Cell, 52, 487 (1988), Eikelenboom et al.,
Acta Neuropathol
., 57, 239 (1982); McGeer et al.,
Canad. J. Neuro. Sci
., 16, 516 (1989), Beyreuther et al.,
Brain Pathol
., 1, 241 (1991); Ishii et al.,
Acta Neuropathol
., 36, 243 (1976). The mechanisms by which these proteins aggregate in the extracellular space to associate with the senile amyloid plaque and congophilic angiopathic lesion are not known. Hence, there is an ongoing need for new ways to investigate and combat this disorder.
SUMMARY OF THE INVENTION
Disclosed is a method of binding a compound to &bgr;-amyloid peptide. The method is based on the finding that the hinge region of antibodies bind to the &bgr;-amyloid peptide. The method comprises the steps of contacting a linker antibody having a hinge region (and preferably at least one antigen binding site) to the &bgr;-amyloid peptide so that the hinge region binds to the &bgr;-amyloid peptide. A compound to be delivered is bound to the antibody before, during, or after the contacting step. In a preferred embodiment the Fc receptor binding region of the linker antibody is deleted.
Where the compound to be delivered is an antigenic compound, the linker antibody is bound with the combining site free, the antibody is selected so that it specifically binds to the compound to be delivered at the combining site, and the antigenic compound is bound to the antigen binding site (before, concurrently with or after the contacting step) so that the antigenic compound is bound to the &bgr;-amyloid peptide.
The method is useful, among other things, for histologic and diagnostic examination of Alzheimer's disease brain tissue, or brain tissue of a patient suspected of being afflicted with Alzheimer's disease, both in vitro and in vivo.
The foregoing and other objects and aspects of the present invention are explained in detail in the specification set forth below.


REFERENCES:
patent: 4271140 (1981-06-01), Bunting
patent: 4891313 (1990-01-01), Berger et al.
patent: 5593846 (1997-01-01), Schenk et al.
patent: WO 91/16819 (1991-11-01), None
patent: WO 92/03474 (1992-03-01), None
Adlersberg, 1976. The immunoglobulin hinge (interdomain) region. La Ricerca Clin. Lab. 6: 191-205.*
Thorpe (1993) Trends in Biotech. 11:40-42.*
Huang et al J. Neuoimmunol. (1993) 48 : 199-204.*
Ishii et al. (1976) Aeta Neuropath. (Beil.) 36:243-249. Sigma Chemical Catalogue (1991), p. 1194.*
Goding (1983) “Monoclonal Antibodies” Academic Press, Orlando, pp. 118-125 and 75-87.*
Roitt (1991) “Essential Immunology”, Blackwell Scientific Publications, Oxford, pp. 35-46.*
Yoshio Namba et al., Apolipoprotein E Immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer's disease and kuru plaque amyloid in Creutzfeldt-Jakob disease,Brain Research541, 163-166 (1991).
T. Wisnicwski and Blas Frangione, Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid,Neuroscience Letters, 135, 235-238 (1992).
Steven G. Younkin, Processing of the Alzheimer's Disease &bgr;A4 Amyloid Protein Precursor (APP),Brain Pathology 1, 253-262 (1991).
John A. Hardy and Gerald A. Higgins, Alzheimer's Disease: The Amyloid Cascade Hypothesis,Science 256, 184-185 (1992).
D. Burdick et al., Assembly and Aggregation Properties of Synthetic Alzheimer's A4/&bgr; Amyloid Peptide Analogs,The Journal of Biological Chemistry 267, 546-554 (1992).
K. Beyreuther and C. L. Masters, Amyloid Precursor Protein (APP) and &bgr;A4 Amyloid in the Etiology of Alzheimer's Disease: Precursor-Product Relationships in the Derangement of Neuronal Function,Brain Pathology 1, 241-251 (1991).
W.J. Strittmatter et al., Apolipoprotein E: High-avidity binding to &bgr;amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease,Proc. Natl. Acad. Sci. USA 901977-1981 (1993).
C.J. Barrow and M.G. Zagorski, Solution Structures of &bgr; Peptide and Its Constituent Fragments: Relation to Amyloid Deposition,Science 253, 179-253 (1991).

Affiliated with

Also associated with

Rating

Method of binding material to the &bgr;-amyloid peptide 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 of binding material to the &bgr;-amyloid peptide, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method of binding material to the &bgr;-amyloid peptide will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2510350