SYNTHETIC IMMUNOGENIC BUT NON-AMYLOIDOGENIC PEPTIDES HOMOLOGOUS TO AMYLOID BETA FOR INDUCTION OF AN IMMUNE RESPONSE TO AMYLOID BETA AND AMYLOID DEPOSITS

• US 20090081204A1
• Filed: 09/19/2008
• Published: 03/26/2009
• Est. Priority Date: 05/22/2000
• Status: Active Grant

• Current Assignee: New York University
• Original Assignee: New York University
• Inventors: FRANGIONE, BLAS, WISNIEWSKI, THOMAS, SIGURDSSON, EINAR M.
• Granted Patent: US 7,700,107 B2
• Time in Patent Office: Days
• US Class Current: 424/130.100
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• 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: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 14/4711 Alzheimer's disease; Amyloid plaque core protein
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention relates to synthetic immunogenic but non-amyloidogenic peptides homologous to amyloid β which can be used alone or conjugated to an immunostimulatory molecule in an immunizing composition for inducing an immune response to amyloid β peptides and amyloid deposits.

Claims

1. A method for inducing an immune response to amyloid β

peptides and amyloid deposits, comprising administering a peptide comprising the amino acid sequence

2. The method of claim 1, wherein the subject is human.

3. The method of claim 1, wherein the peptide comprises an N-terminal, C-terminal, or both N- and C-terminal, polylysine or polyaspartate sequence of 4-10 residues.

4. The method of claim 1, comprising administering a conjugate comprising the peptide and a polymer.

5. A molecule comprising the antigen-binding portion of an antibody raised against a peptide comprising the amino acid sequence (Asp Ala Glu Phe Arg His Asp Ser Gly Tyr Glu Val His His Gln Lys Xaa₁ Xaa₂ Xaa₃ Xaa₄ Xaa₅ Glu Asp Val Gly Ser Asn Lys Gly Ala), (SEQ ID NO:

15)

wherein n is 1 or 2; and

Xaa₁, Xaa₂, Xaa₃, Xaa₄, and Xaa₅ are Leu, Val, Phe, Phe, and Ala, respectively, in which one or two of residues Xaa₁, Xaa₂, Xaa₃, Xaa₄, and Xaa₅ is substituted with Lys, Asp, or Glu.

6. The molecule of claim 5, wherein the molecule is a monoclonal antibody.

7. The molecule of claim 5, wherein the molecule is a chimeric or humanized antibody.

8. A pharmaceutical composition comprising the molecule of claim 5 and a pharmaceutically acceptable carrier, diluent, excipient or auxiliary agent.

9. A method for reducing the formation of amyloid fibrils and deposits, comprising administering the molecule of claim 5 to a subject in need thereof.

10-15. -15. (canceled)

21-22. -22. (canceled)