Single chain antibodies against β-amyloid peptide

• US 8,124,076 B2
• Filed: 08/18/2006
• Issued: 02/28/2012
• Est. Priority Date: 08/18/2005
• Status: Expired due to Fees

• Current Assignee: Ramot at Tel Aviv University Limited (Tel Aviv University)
• Original Assignee: Ramot at Tel Aviv University Limited (Tel Aviv University)
• Inventors: Solomon, Beka, Cohen-Kupiec, Rachel
• Primary Examiner(s): Kolker, Daniel E
• Assistant Examiner(s): Gucker, Stephen
• Application Number:
  US12/064,144
• Publication Number:
  US 20090186027A1
• Time in Patent Office: 2,020 Days
• Field of Search: None
• US Class Current: 424/130.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• 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 2317/569 Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/70 characterized by effect upon binding to a cell or to an antigen

Abstract

Anti-AβP scFvs and single domain antibodies were generated, and when these antibodies were displayed on filamentous phage or as soluble protein molecules, stabilized by the maltose binding protein, they could prevent the fibrilization of Abp 1-40 and disaggregate Abp 1-40 fibrils generated in vitro. The anti-Aβp scFv antibodies also stained amyloid neuritic plaques on slices from transgenic mice. The anti-AβP scFv and single domain antibodies can be used for inhibiting or treating Alzheimer'"'"'s disease.

Claims

1. An antibody against β

-amyloid peptide, comprising the complementarity-determining regions (CDRs) of an antibody heavy chain or light chain selected from the group of CDR1, CDR2 and CDR3 sequences consisting of;

(1) SEQ ID NOs;

10, 12 and 14; and

(2) SEQ ID Nos;

16, 18 and 20.

2. The antibody of claim 1, which is a single domain antibody.

3. The antibody of claim 2, wherein the single domain comprises the CDR sequences of SEQ ID Nos:

10, 12 and 14.

4. The antibody of claim 3, wherein the single domain comprises the amino acid sequence of residues 1 to 124 of SEQ ID NO:

6.

5. The antibody of claim 2, wherein the single domain comprises the CDR sequences of SEQ ID Nos:

16, 18 and 20.

6. The antibody of claim 5, wherein the single domain comprises the amino acid sequence of residues 140 to 247 of SEQ ID NO:

6.

7. The antibody of claim 1, which is a single chain (scFv) antibody.

8. The antibody of claim 7, comprising the CDR sequences of SEQ ID Nos:

10, 12, 14, 16, 18 and 20.

9. The antibody of claim 8, comprising the amino acid sequence of SEQ ID NO:

6.

10. A pharmaceutical composition comprising an effective amount of the antibody of claim 1 and a pharmaceutically acceptable carrier, diluent, excipient or auxillary agent.

11. A method reducing β

-amyloid plaque load in the brain, for comprising administering the antibody of claim 1 to a patient in need thereof.

12. The method of claim 11, wherein the antibody is administered intranasally.