Method of screening an antibody for activity in clearing an amyloid deposit

• US 7,575,880 B1
• Filed: 11/28/2000
• Issued: 08/18/2009
• Est. Priority Date: 05/26/2000
• Status: Expired due to Fees

• Current Assignee: Janssen Alzheimer Immunotherapy (Johnson & Johnson)
• Original Assignee: Elan Pharma International Limited (Perrigo Company PLC)
• Inventors: Bard, Frederique, Schenk, Dale B., Yednock, Theodore
• Primary Examiner(s): Kolker; Daniel E.
• Application Number:
  US09/724,288
• Time in Patent Office: 3,185 Days
• Field of Search: 435/7.1, 435/7.2, 435/7.24, 435/7.21, 736/536
• US Class Current: 435/7.21
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/77 Internalization into the cell

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.

Claims

1. A method of screening a monoclonal antibody for activity in inducing clearance of an amyloid deposit of Aβ

, comprising;

combining the amyloid deposit, a monoclonal antibody which binds to an epitope within amino acid residues 1-7 of Aβ

, and microglial cells bearing Fc receptors in a medium in vitro; and

by a series of measurements, monitoring whether a reduction in the amount of the amyloid deposit remaining in the medium occurs, as compared to a baseline measurement, a reduction in the amount of the amyloid deposit indicating the monoclonal antibody induces phagocytic clearing activity of the microglial cells against the amyloid deposit.

2. The method of claim 1, wherein the combining step comprises combining the amyloid deposit and the antibody before adding the microglial cell bearing Fc receptors.

3. A method of screening a monoclonal antibody for activity in inducing clearance of an amyloid deposit of Aβ

, comprising;

combining the amyloid deposit, a monoclonal antibody, and microglial cells bearing Fc receptors in a medium in vitro, wherein the amyloid deposit is a tissue sample from the brain of an Alzheimer'"'"'s disease patient or an animal having Alzheimer'"'"'s pathology; and

by a series of measurements, monitoring whether a reduction in the amount of the amyloid deposit remaining in the medium occurs, as compared to a baseline measurement, a reduction in the amount of the amyloid deposit indicating the monoclonal antibody induces phagocytic clearing activity of the microglial cells against the amyloid deposit.

4. The method of claim 3, wherein the combining step comprises combining the tissue sample and the antibody before adding the microglial cells bearing Fc receptors.