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a technology of amyloidogenic disease and amyloid aggregation, which is applied in the field of immunology and medicine, can solve the problem of implausible therapeutic benefi
Inactive Publication Date: 2005-06-30
JANSSEN ALZHEIMER IMMUNOTHERAPY
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[0008] In one aspect, the invention provides methods of preventing or treating a disease associated with amyloid deposits of Aβ in the brain of a patient. Such diseases include Alzheimer's disease, Down's syndrome and cognitive impairment. The latter can occur with or without other characteristics of an amyloidogenic disease. Some methods of the invention entail administering an effective dosage of an antibody that specifically binds to a component of an amyloid deposit to the patient. Such methods are particularly useful for preventing or treating Alzheimer's disease in human patients. Some methods entail administering an effective dosage of an antibody that binds to Aβ. Some methods entail administering an effective dosage of an antibody that specifically binds to an epitope within residues 1-10 of Aβ. In some methods, the antibody specifically binds to an epitope within r
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Because EP 526,511 's proposed dosage would barely alter the level of endogenous circulating Aβ and because EP 526,511 doe
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I. Prophylactic Efficacy of Aβ Against AD
[0198] These examples describe administration of Aβ42 peptide to transgenic mice overexpressing APP with a mutation at position 717 (APP717V→F) that predisposes them to develop Alzheimer's-like neuropathology. Production and characteristics of these mice (PDAPP mice) is described in Games et al., Nature, supra. These animals, in their heterozygote form, begin to deposit Aβ at six months of age forward. By fifteen months of age they exhibit levels of Aβ deposition equivalent to that seen in Alzheimer's disease. PDAPP mice were injected with aggregated Aβ42 (aggregated Aβ42) or phosphate buffered saline. Aggregated Aβ42 was chosen because of its ability to induce antibodies to multiple epitopes of Aβ.
[0199] A. Methods
[0200] 1. Source of Mice
[0201] Thirty PDAPP heterogenic female mice were randomly divided into the following groups: 10 mice to be injected with aggregated Aβ42 (one died in transit), 5 mice to be injected with PBS / adjuvant or...
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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.
Description
CROSS-REFERENCES TO RELATED APPLICATIONS [0001] This application is a continuation of U.S. application Ser. No. 10 / 889,999, filed Jul. 12, 2004, which is a continuation of U.S. application Ser. No. 09 / 580,018, filed May 26, 2000, which is a continuation-in-part of U.S. application Ser. No. 09 / 322,289, filed May 28, 1999, which is a continuation-in-part of U.S. application Ser. No. 09 / 201,430, filed Nov. 30, 1998, which claims the benefit under 35 U.S.C. § 119(e) of U.S. Application No. 60 / 080,970, filed Apr. 7, 1998 and U.S. Application No. 60 / 067,740, filed Dec. 2, 1997, each of which is incorporated herein by reference in its entirety for all purposes. This application is also a continuation of U.S. application Ser. No. 10 / 09 / 724,940, filed Nov. 28, 2000, which is a continuation of U.S. application Ser. No. 09 / 580,015, filed May 26, 2000, which is a continuation-in-part of U.S. application Ser. No. 09 / 322,289, filed May 28, 1999, which is a continuation-in-part of U.S. application...
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