Assay method for Alzheimer's disease

• US 8,444,977 B2
• Filed: 07/12/2010
• Issued: 05/21/2013
• Est. Priority Date: 08/17/2001
• Status: Expired due to Term

• Current Assignee: Eli Lilly and Company, Washington University In St Louis
• Original Assignee: Eli Lilly and Company, Washington University In St Louis
• Inventors: Holtzman, David M., DeMattos, Ronald, Bales, Kelly R., Cummins, David J., Paul, Steven M.
• Primary Examiner(s): Kemmerer, Elizabeth C
• Assistant Examiner(s): BALLARD, KIMBERLY
• Application Number:
  US12/834,271
• Publication Number:
  US 20100279433A1
• Time in Patent Office: 1,044 Days
• Field of Search: None
• US Class Current: 424/139.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/41 Glycosylation, sialylation, or fucosylation
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: G01N 2800/2821 Alzheimer
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

A diagnostic test for preclinical and clinical Alzheimer'"'"'s disease is based on plasma levels of Aβ₄₀, Aβ₄₂, their ratio, or their rate of entry following administration of antibodies that sequester Aβ. Alterations of any of these parameters from control values identifies preclinical or clinical Alzheimer'"'"'s disease.

Claims

1. A method for diagnosing a condition associated with Aβ

deposits in a subject comprising the steps of;

(a) administering to the subject an amount of an antibody which specifically binds an epitope contained within positions 13-28 of Aβ

;

(b) measuring the level of Aβ

₄₀ in a blood sample obtained from the subject at a time interval after the administering step; and

(c) comparing the measured level of Aβ

₄₀ in the subject with a control value, wherein an altered measured level of Aβ

₄₀ in the subject as compared to the control value identifies the subject as having a condition associated with Aβ

deposits.

2. The method of claim 1, wherein the time interval is less than 1 week.

3. The method of claim 1, wherein the time interval is less than or equal to 24 hours.

4. The method of claim 1, wherein the time interval is less than or equal to 3 hours.

5. The method of claim 1, wherein the subject is human and the antibody is a humanized antibody or an epitope-binding fragment thereof.

6. The method of claim 5, wherein the humanized antibody or epitope-binding fragment thereof comprises a light chain of the sequence given by SEQ ID NO:

11 and a heavy chain of the sequence given by SEQ ID NO;

12.

7. The method of claim 5, wherein the humanized antibody or epitope-binding fragment thereof comprises a light chain of the sequence given by SEQ ID NO:

11 and a heavy chain of the sequence given by SEQ ID NO;

16.

8. The method of claim 5, wherein the humanized antibody or epitope-binding fragment thereof comprises a light chain comprising a variable region of the sequence given by SEQ ID NO:

7 and a heavy chain comprising a variable region of the sequence given by SEQ ID NO;

14.

9. The method of claim 5, wherein the humanized antibody or epitope-binding fragment thereof comprises:

a. a light chain comprising three light chain complementarity determining regions (CDRs) having the following amino acid sequences;

10. The method of claim 1, wherein the antibody is an epitope-binding fragment thereof.

11. The method of claim 1, wherein the antibody is a single-chain antibody.

12. The method of claim 1, wherein the condition associated with Aβ

deposits is Down'"'"'s syndrome, preclinical cerebral amyloid angiopathy, or clinical cerebral amyloid angiopathy.