Prevention and treatment of amyloidogenic disease
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Accused Products
Abstract
The invention provides improved agents and methods for treatment of diseases associated with amyloid deposits of Aβ in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the amyloid deposit. The methods are useful for prophylactic and therapeutic treatment of Alzheimer'"'"'s disease. Preferred agents including N-terminal fragments of Aβ and antibodies binding to the same.
183 Citations
118 Claims
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1-68. -68. (Canceled).
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69. A chimeric peptide comprising:
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a peptide having a first portion and a second portion, wherein the carboxyl terminus of the first portion is linked to the amino terminus of the second portion; and
,wherein the first portion is from the free N-terminus of a naturally-occurring internal peptide cleavage product which, when naturally-occurring in a mammal, is derived from a precursor protein or a mature protein and the second portion comprises a T helper cell epitope;
or,wherein the first portion comprises a T helper cell epitope and the second portion is from the free C-terminus of said naturally-occurring internal peptide cleavage product. - View Dependent Claims (70, 71, 72, 73, 74, 75, 76, 77, 78)
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79. A method for in vivo down-regulation of beta amyloid (Aβ
- ) in a patient, including a human being, the method comprising effecting presentation to the patient'"'"'s immune system of an immunogenically effective amount of at least one analog of Aβ
that incorporates into the same molecule at least one B-cell epitope of Aβ and
at least one foreign T-helper epitope (TH epitope) so that immunization of the animal with the analog induces production of antibodies against the patient'"'"'s endogenous Aβ
, wherein the analoga) is a polyamino acid that consists of at least one copy of a subsequence of Aβ
, wherein the foreign TH epitope is incorporated by means of amino acid addition and/or insertion and/or deletion and/or substitution, wherein the subsequence is selected from the group consisting of residues 1-42, residues 1-40, residues 1-39, residues 1-28, residues 1-12, residues 1-5, residues 13-28, residues 17-28, residues 25-35, residues 35-40, and residues 35-42 of Aβ
; and
/orb) is a polyamino acid that contains the foreign TH epitopes and a disrupted Aβ
sequence so that the analog does not include any subsequence of Aβ
that binds productively to MHC class II molecules initiating a T-cell response; and
/orc) is a polyamino acid that comprises the foreign TH epitope and Aβ
derived amino acids, and comprises a conservative substitution. - View Dependent Claims (80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118)
- ) in a patient, including a human being, the method comprising effecting presentation to the patient'"'"'s immune system of an immunogenically effective amount of at least one analog of Aβ
Specification